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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="TANGO2 Deficiency" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2023/03/09" /><meta name="citation_author" content="Christina Y Miyake" /><meta name="citation_author" content="Lindsay Burrage" /><meta name="citation_author" content="Kevin Glinton" /><meta name="citation_author" content="Kimberly Houck" /><meta name="citation_author" content="Alfonso Hoyos-Martinez" /><meta name="citation_author" content="Brett Graham" /><meta name="citation_author" content="Yaping Yang" /><meta name="citation_author" content="Brandy Rawls-Castillo" /><meta name="citation_author" content="Fernando Scaglia" /><meta name="citation_author" content="Claudia Soler-Alfonso" /><meta name="citation_author" content="Seema R Lalani" /><meta name="citation_pmid" content="29369572" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK476443/" /><meta name="citation_keywords" content="TANGO2 Deficiency Disorder" /><meta name="citation_keywords" content="TANGO2-Related Metabolic Encephalopathy and Arrhythmias" /><meta name="citation_keywords" content="TANGO2 Deficiency Disorder" /><meta name="citation_keywords" content="TANGO2-Related Metabolic Encephalopathy and Arrhythmias" /><meta name="citation_keywords" content="Transport and Golgi organization protein 2 homolog" /><meta name="citation_keywords" content="TANGO2" /><meta name="citation_keywords" content="TANGO2 Deficiency" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="TANGO2 Deficiency" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Christina Y Miyake" /><meta name="DC.Contributor" content="Lindsay Burrage" /><meta name="DC.Contributor" content="Kevin Glinton" /><meta name="DC.Contributor" content="Kimberly Houck" /><meta name="DC.Contributor" content="Alfonso Hoyos-Martinez" /><meta name="DC.Contributor" content="Brett Graham" /><meta name="DC.Contributor" content="Yaping Yang" /><meta name="DC.Contributor" content="Brandy Rawls-Castillo" /><meta name="DC.Contributor" content="Fernando Scaglia" /><meta name="DC.Contributor" content="Claudia Soler-Alfonso" /><meta name="DC.Contributor" content="Seema R Lalani" /><meta name="DC.Date" content="2023/03/09" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK476443/" /><meta name="description" content="TANGO2 deficiency is characterized by developmental delay, intellectual disability, gait incoordination, speech difficulties, seizures, and hypothyroidism. Most individuals have TANGO2 spells, non-life-threatening paroxysmal worsening of baseline symptoms, including sudden onset of hypotonia, ataxia with loss of balance, head and body tilt, increased dysarthria, drooling, lethargy, and disorientation. In addition, life-threatening acute metabolic crises can occur, including rhabdomyolysis with elevated creatine phosphokinase and liver transaminases, hypoglycemia, prolonged QTc on EKG, ventricular arrhythmias, and/or cardiomyopathy." /><meta name="og:title" content="TANGO2 Deficiency" /><meta name="og:type" content="book" /><meta name="og:description" content="TANGO2 deficiency is characterized by developmental delay, intellectual disability, gait incoordination, speech difficulties, seizures, and hypothyroidism. 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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK476443_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK476443_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/iiae3/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/tardbp-als/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK476443_"><span class="title" itemprop="name">TANGO2 Deficiency</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: TANGO2 Deficiency Disorder, <i>TANGO2</i>-Related Metabolic Encephalopathy and Arrhythmias</div><p class="contrib-group"><span itemprop="author">Christina Y Miyake</span>, MD, MS, <span itemprop="author">Lindsay Burrage</span>, MD, PhD, <span itemprop="author">Kevin Glinton</span>, MD, PhD, <span itemprop="author">Kimberly Houck</span>, MD, <span itemprop="author">Alfonso Hoyos-Martinez</span>, MD, <span itemprop="author">Brett Graham</span>, MD, PhD, <span itemprop="author">Yaping Yang</span>, PhD, <span itemprop="author">Brandy Rawls-Castillo</span>, MS, RD, LD, <span itemprop="author">Fernando Scaglia</span>, MD, <span itemprop="author">Claudia Soler-Alfonso</span>, MD, and <span itemprop="author">Seema R Lalani</span>, MD.</p><a data-jig="ncbitoggler" href="#__NBK476443_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK476443_ai__"><div class="contrib half_rhythm"><span itemprop="author">Christina Y Miyake</span>, MD, MS<div class="affiliation small">Associate Professor, Department of Pediatrics<br />Section of Cardiology<br />Associate Professor<br />Molecular Physiology and Biophysics<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.mcb@ekayimyc" class="oemail">ude.mcb@ekayimyc</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Lindsay Burrage</span>, MD, PhD<div class="affiliation small">Associate Professor, Department of Molecular and Human Genetics<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.mcb@egarrub" class="oemail">ude.mcb@egarrub</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Kevin Glinton</span>, MD, PhD<div class="affiliation small">Assistant Professor, Department of Molecular and Human Genetics<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.mcb@notnilG.niveK" class="oemail">ude.mcb@notnilG.niveK</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Kimberly Houck</span>, MD<div class="affiliation small">Assistant Professor, Department of Neurology<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.snerdlihcsaxet@kcuohmk" class="oemail">gro.snerdlihcsaxet@kcuohmk</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Alfonso Hoyos-Martinez</span>, MD<div class="affiliation small">Assistant Professor, Department of Pediatrics<br />Division of Pediatric Diabetes and Endocrinology<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.snerdlihcsaxet@msoyohxa" class="oemail">gro.snerdlihcsaxet@msoyohxa</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Brett Graham</span>, MD, PhD<div class="affiliation small">Associate Professor, Department of Molecular and Human Genetics<br />Indiana University School of Medicine<br />Indianapolis, Indiana<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.ui@ahargerb" class="oemail">ude.ui@ahargerb</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Yaping Yang</span>, PhD<div class="affiliation small">AiLife Diagnostics<br />Pearland, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.suefilia@ygnipay" class="oemail">moc.suefilia@ygnipay</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Brandy Rawls-Castillo</span>, MS, RD, LD<div class="affiliation small">Clinical Program Coordinator<br />Clinical Dietitian<br />Department of Molecular and Human Genetics<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.snerdlihcsaxet@slwarlb" class="oemail">gro.snerdlihcsaxet@slwarlb</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Fernando Scaglia</span>, MD<div class="affiliation small">Professor<br />Department of Molecular and Human Genetics<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.mcb@ailgacsf" class="oemail">ude.mcb@ailgacsf</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Claudia Soler-Alfonso</span>, MD<div class="affiliation small">Assistant Professor, Department of Molecular and Human Genetics<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.mcb@relos" class="oemail">ude.mcb@relos</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Seema R Lalani</span>, MD<div class="affiliation small">Professor<br />Department of Molecular and Human Genetics<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.cmt.mcb@lamees" class="oemail">ude.cmt.mcb@lamees</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">January 25, 2018</span>; Last Update: <span itemprop="dateModified">March 9, 2023</span>.</p><p><em>Estimated reading time: 29 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="tango2-mea.Summary" itemprop="description"><h2 id="_tango2-mea_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>TANGO2 deficiency is characterized by developmental delay, intellectual disability, gait incoordination, speech difficulties, seizures, and hypothyroidism. Most individuals have TANGO2 spells, non-life-threatening paroxysmal worsening of baseline symptoms, including sudden onset of hypotonia, ataxia with loss of balance, head and body tilt, increased dysarthria, drooling, lethargy, and disorientation. In addition, life-threatening acute metabolic crises can occur, including rhabdomyolysis with elevated creatine phosphokinase and liver transaminases, hypoglycemia, prolonged QTc on EKG, ventricular arrhythmias, and/or cardiomyopathy.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of TANGO2 deficiency is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in <i>TANGO2</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p></div><div><h4 class="inline">Management.</h4><p><i>Targeted therapy:</i> Daily supplementation with a multivitamin including all eight B vitamins or a B-complex vitamin at the minimum recommended daily allowance for age.</p><p><i>Supportive care:</i> Treatment of acute metabolic crises: admission to ICU for individuals who are ill appearing with elevated CK, hypoglycemia, or have prolonged QTc; intravenous (IV) hydration with glucose-containing fluids for hypoglycemia; echocardiogram to assess cardiac function with adjustment of IV fluids to prevent pulmonary edema; potassium supplements as needed; supplemental magnesium to maintain magnesium >2.2 mg/dL to minimize arrhythmias; nutrition support with vitamin supplementation including all eight B vitamins; monitor creatine phosphokinase; EKG to monitor QTc and for development of type 1 Brugada pattern; continuous rhythm monitoring for arrhythmias including premature ventricular contractions, ventricular tachycardia, and torsade de pointes; extracorporeal membrane oxygenation only as needed; levothyroxine as needed for hypothyroidism. Due to the recalcitrant nature of ventricular arrhythmias, management by an electrophysiologist is recommended.</p><p>Treatment of non-acute presentation: developmental and educational support; anti-seizure medication for seizures; levothyroxine for hypothyroidism; feeding therapy and/or gastrostomy tube feeding as needed; standard treatments for constipation.</p><p><i>Surveillance:</i> Developmental assessment at each visit; assess vitamin B complex intake at each visit; measure vitamin B<sub>6</sub> serum level as needed to prevent toxicity; EKG, Holter, and echocardiogram with frequency based on history of metabolic and cardiac crises; neurologic follow up to monitor those with seizures; annual TSH and free T4 for hypothyroidism; ophthalmologic follow up as recommended by ophthalmologist; gastrointestinal and nutrition assessments as needed; assessment of hearing loss as needed; assess family and social work needs at each visit.</p><p><i>Agents/circumstances to avoid:</i> Triggers for TANGO2 spells and acute metabolic crises including fasting, dehydration, overexertion, exposure to excessive heat, ketogenic diet, and infections.</p><p><i>Evaluation of relatives at risk:</i> It is appropriate to clarify the genetic status of apparently asymptomatic older and younger sibs of an affected individual by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> to allow prompt initiation of B-complex vitamins, supportive treatment, and avoidance of triggers for TANGO2 spells and acute metabolic crises.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>TANGO2 deficiency is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner. If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>TANGO2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of inheriting neither of the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pathogenic variants. Once the <i>TANGO2</i> pathogenic variants have been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/carrier-testing/">carrier testing</a> for at-risk relatives and prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p></div></div><div id="tango2-mea.Diagnosis"><h2 id="_tango2-mea_Diagnosis_">Diagnosis</h2><div id="tango2-mea.Suggestive_Findings"><h3>Suggestive Findings</h3><p>TANGO2 deficiency should be suspected in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with the following clinical, laboratory, EKG, imaging, and family history findings.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Developmental delay (including motor and speech delays)</div></li><li class="half_rhythm"><div>Spasticity</div></li><li class="half_rhythm"><div>Poor coordination and unsteady gait</div></li><li class="half_rhythm"><div>Speech difficulties (dysarthria, slurred or nasal speech)</div></li><li class="half_rhythm"><div>Intellectual disability</div></li><li class="half_rhythm"><div>Paroxysmal neurologic episodes (TANGO2 spells). Sudden onset of clumsy gait, falling, head tilt, body tilt, dystonia, abnormal posturing with hypertonicity, dysarthria, drooling, extreme fatigue, and disorientation</div></li><li class="half_rhythm"><div>Acute metabolic crises. Rhabdomyolysis with muscle weakness, pain, or dark urine; ataxia, disorientation or coma, and developmental regression</div></li><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>Exotropia</div></li><li class="half_rhythm"><div>Constipation</div></li><li class="half_rhythm"><div>TANGO2 spells or acute metabolic crisis in an individual with <a href="/books/n/gene/gr_22q11deletion/">22q11.2 deletion syndrome</a></div></li></ul><p>
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<b>Laboratory findings</b>
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</p><ul><li class="half_rhythm"><div>During acute metabolic crises, elevated creatine phosphokinase, alanine transaminase, and aspartate transaminase, hypoglycemia, mild lactic acidosis, and mild hyperammonemia</div></li><li class="half_rhythm"><div>Hypothyroidism with elevated thyroid-stimulating hormone and low thyroxine</div></li></ul><p><b>EKG findings.</b> During acute metabolic crisis, QTc prolongation with or without type 1 Brugada pattern. Note: EKG will normalize when crisis resolves.</p><p><b>Imaging findings on brain MRI.</b> Diffuse ventriculomegaly, cerebral volume loss, and diminished white matter have been observed.</p><p><b>Family history</b> is consistent with <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> inheritance (e.g., affected sibs and/or parental <a class="def" href="/books/n/gene/glossary/def-item/consanguinity/">consanguinity</a>). Absence of a known family history does not preclude the diagnosis.</p></div><div id="tango2-mea.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of TANGO2 deficiency <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with <a href="#tango2-mea.Suggestive_Findings">suggestive findings</a> and <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variants in <i>TANGO2</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK476443/table/tango2-mea.T.molecular_genetic_testing_u/?report=objectonly" target="object" rid-ob="figobtango2meaTmoleculargenetictestingu">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "<a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>" and "<a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a> variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bk_pop" href="#tango2-mea.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include any likely pathogenic variants. (2) Identification of <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>TANGO2</i> variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> (or of one known <i>TANGO2</i> pathogenic variant and one <i>TANGO2</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b><a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted testing</b> (single-gene testing, <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a>) and <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (<a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>, <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>) depending on the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>.</p><p>Gene-targeted testing requires that the clinician determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> is likely involved, whereas <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing does not. Individuals with the distinctive findings of rhabdomyolysis, cardiac arrhythmias, and/or TANGO2 spells in the setting of neurodevelopmental delay are likely to be diagnosed using gene-targeted testing (see <a href="#tango2-mea.Option_1">Option 1</a>), whereas those with a <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> indistinguishable from many other neurodevelopmental disorders are more likely to be diagnosed using genomic testing (see <a href="#tango2-mea.Option_2">Option 2</a>).</p><div id="tango2-mea.Option_1"><h4>Option 1</h4><p><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b>. Sequence analysis and <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> of <i>TANGO2</i>.</p><p>Note: Targeted analysis for pathogenic variants can be performed first in selected populations if resources are limited.</p><ul><li class="half_rhythm"><div>In individuals of Hispanic ethnicity from Latin America, targeted analysis for <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> c.460G>A (p.Gly154Arg) and the ~34-kb <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> encompassing exons 3-9 can be performed.</div></li><li class="half_rhythm"><div>In individuals of European ancestry, targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> analysis for the ~34-kb deletion encompassing exons 3-9 can be performed.</div></li></ul><p><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>TANGO2</i> and other genes of interest (see <a href="#tango2-mea.Differential_Diagnosis">Differential Diagnosis</a>) may also be considered to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="tango2-mea.Option_2"><h4>Option 2</h4><p><b>Comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> is likely involved. <b>Exome sequencing</b> and <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> may be considered.</p><p>For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div id="tango2-mea.T.molecular_genetic_testing_u" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in TANGO2 Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.T.molecular_genetic_testing_u/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.T.molecular_genetic_testing_u_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tango2-mea.T.molecular_genetic_testing_u_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_tango2-mea.T.molecular_genetic_testing_u_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_tango2-mea.T.molecular_genetic_testing_u_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Identified by Method</th></tr></thead><tbody><tr><td headers="hd_h_tango2-mea.T.molecular_genetic_testing_u_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TANGO2</i>
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</td><td headers="hd_h_tango2-mea.T.molecular_genetic_testing_u_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_tango2-mea.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~40% <sup>4, 5</sup></td></tr><tr><td headers="hd_h_tango2-mea.T.molecular_genetic_testing_u_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>6</sup></td><td headers="hd_h_tango2-mea.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~60% <sup>4, 5</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="tango2-mea.TF.1.1"><p class="no_margin">See <a href="/books/NBK476443/#tango2-mea.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>2. </dt><dd><div id="tango2-mea.TF.1.2"><p class="no_margin">See <a href="#tango2-mea.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p></div></dd><dt>3. </dt><dd><div id="tango2-mea.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants and small intragenic deletions/insertions; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>4. </dt><dd><div id="tango2-mea.TF.1.4"><p class="no_margin">Detection rate varies with the ethnicity of the individual being tested.</p></div></dd><dt>5. </dt><dd><div id="tango2-mea.TF.1.5"><p class="no_margin"><a class="bk_pop" href="#tango2-mea.REF.kremer.2016.358">Kremer et al [2016]</a>, <a class="bk_pop" href="#tango2-mea.REF.lalani.2016.347">Lalani et al [2016]</a>, <a class="bk_pop" href="#tango2-mea.REF.dines.2019.601">Dines et al [2019]</a>, <a class="bk_pop" href="#tango2-mea.REF.miyake.2023.100352">Miyake et al [2023]</a></p></div></dd><dt>6. </dt><dd><div id="tango2-mea.TF.1.6"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd></dl></div></div></div></div></div></div><div id="tango2-mea.Clinical_Characteristics"><h2 id="_tango2-mea_Clinical_Characteristics_">Clinical Characteristics</h2><div id="tango2-mea.Clinical_Description"><h3>Clinical Description</h3><p>TANGO2 deficiency is characterized by developmental delay, intellectual disability, TANGO2 spells, acute metabolic crises, and risk of cardiac crisis. Additional features can include seizures, hypothyroidism, exotropia, and constipation. To date, more than 100 individuals have been identified with <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> pathogenic variants in <i>TANGO2</i> [<a class="bk_pop" href="#tango2-mea.REF.kremer.2016.358">Kremer et al 2016</a>, <a class="bk_pop" href="#tango2-mea.REF.lalani.2016.347">Lalani et al 2016</a>, <a class="bk_pop" href="#tango2-mea.REF.dines.2019.601">Dines et al 2019</a>, <a class="bk_pop" href="#tango2-mea.REF.powell.2021.34">Powell et al 2021</a>, <a class="bk_pop" href="#tango2-mea.REF.schymick.2022.473">Schymick et al 2022</a>, <a class="bk_pop" href="#tango2-mea.REF.miyake.2023.100352">Miyake et al 2023</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div id="tango2-mea.T.tango2_deficiency_disorder" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>TANGO2 Deficiency Disorder: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.T.tango2_deficiency_disorder/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.T.tango2_deficiency_disorder_lrgtbl__"><table><thead><tr><th id="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature</th><th id="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Developmental delay</b>
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</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">99%</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically both motor & speech</td></tr><tr><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Speech difficulties</b>
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</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">97%</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dysarthria, slurred or nasal speech</td></tr><tr><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Intellectual disability</b>
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</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">97%</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically mild to moderate</td></tr><tr><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>TANGO2 spells</b>
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</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">94%</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Loss of balance, head & body tilt, dystonia, dysarthria, drooling, & lethargy</td></tr><tr><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Acute metabolic crises</b>
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||
</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~66%</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rhabdomyolysis, prolonged QTc on EKG</td></tr><tr><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cardiac crises</b>
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||
</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">41%</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ventricular arrhythmias, cardiomyopathy, & cardiac arrest</td></tr><tr><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Seizures</b>
|
||
</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">40%-50%</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Brain imaging abnormalities</b>
|
||
</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~60%</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Diffuse ventriculomegaly, cerebral volume loss, & diminished white matter</td></tr><tr><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hypothyroidism</b>
|
||
</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">40%-50%</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Exotropia</b>
|
||
</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">60%</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Constipation</b>
|
||
</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">50%</td><td headers="hd_h_tango2-mea.T.tango2_deficiency_disorder_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div></div><p><b>Motor delays</b> are generally seen by age one to two years. The median age of walking is about 16 months. Regression of developmental milestones such as walking is common after a metabolic crisis. Some individuals never achieve ambulation after an early metabolic crisis.</p><p>Spasticity of lower extremities, hyperreflexia, and clonus are also frequently seen. Poor coordination, progressively unsteady gait, and clumsiness are frequently reported in ambulatory individuals, even prior to the first episode of rhabdomyolysis [<a class="bk_pop" href="#tango2-mea.REF.powell.2021.34">Powell et al 2021</a>, <a class="bk_pop" href="#tango2-mea.REF.schymick.2022.473">Schymick et al 2022</a>, <a class="bk_pop" href="#tango2-mea.REF.miyake.2023.100352">Miyake et al 2023</a>].</p><p><b>Speech delay/difficulties.</b> Speech delay is common. There is variability in expressive language delay, with some individuals able to speak easily and others being nonverbal. Individuals who have had significant developmental regression secondary to metabolic crises can have severe language impairment.</p><p>Almost all individuals with TANGO2 deficiency have speech difficulties, including dysarthria and slurred or nasal speech.</p><p><b>Intellectual disability</b> of variable severity is observed in almost all individuals. Most individuals have mild-to-moderate intellectual disability, although some have severe cognitive impairment.</p><p><b>TANGO2 spells</b> (non-life-threatening paroxysmal neurologic episodes) occur in most individuals with TANGO2 deficiency. Onset is typically between ages one and three years. TANGO2 spells can be recognized by the sudden onset of hypotonia with loss of muscle control (e.g., clumsy gait, sudden falling while walking or sitting, inability to upright themselves after falling), head tilt (either to the side or back), body tilt, dystonia, abnormal posturing with hypertonicity, increased dysarthria, drooling, extreme fatigue, and disorientation. The episodes usually last for minutes to hours but can last for days and tend to resolve with rest. Episodes occur most often in the morning upon awakening, after exertion, and with decreased oral intake, illness, and exposure to warmer weather. TANGO2 spells can occur throughout life but are more common in toddlers and may increase during puberty. TANGO2 spells are not associated with metabolic derangements such as elevated creatine phosphokinase (CK), alanine transaminase (ALT), and aspartate transaminase (AST) and/or hypoglycemia; EKG changes do not occur during TANGO2 spells [<a class="bk_pop" href="#tango2-mea.REF.miyake.2023.100352">Miyake et al 2023</a>].</p><p><b>Acute metabolic crises.</b> The acute presentation varies from significant muscle weakness and/or pain, ataxia, and disorientation to a comatose state. Acute metabolic crises are frequently precipitated by reduced oral intake or fasting, dehydration, or febrile illness. Cryptic infections such as a tooth abscess can trigger an acute metabolic crisis. In a natural history study of 73 individuals with TANGO2 deficiency, approximately two thirds of individuals presented in acute metabolic crisis, with the first episode occurring at a median age of three years (range: age five months to 20 years) [<a class="bk_pop" href="#tango2-mea.REF.miyake.2022.1673">Miyake et al 2022</a>].</p><p>Individuals present with rhabdomyolysis with elevated CK, ALT, and AST and may have dark urine due to myoglobinuria. Complications from rhabdomyolysis are not common, even though CK levels can be significantly elevated in some individuals (>200,000 U/L). Severe hypoglycemia can be present in addition to mild hyperammonemia, elevated aldolase, elevated troponin, elevated lactate, and evidence of ketoacidosis and lactic acidosis on urine organic acids. Although an acylcarnitine profile during an acute metabolic crisis may show elevated C14:1, C14:2, and C16:1, no consistent acylcarnitine abnormalities have been identified in large studies [<a class="bk_pop" href="#tango2-mea.REF.b_rat.2021.415">Bérat et al 2021</a>, <a class="bk_pop" href="#tango2-mea.REF.schymick.2022.473">Schymick et al 2022</a>, <a class="bk_pop" href="#tango2-mea.REF.miyake.2023.100352">Miyake et al 2023</a>].</p><p>While cardiac workup including EKG is normal at baseline, during an acute metabolic crisis, EKG changes are noted. The most common EKG finding is prolonged QTc that is often markedly prolonged (>500 msec). Transient type 1 Brugada pattern can also be seen in 33% of individuals.</p><p>B-complex vitamins or multivitamins may prevent metabolic crises in individuals with TANGO2 deficiency [<a class="bk_pop" href="#tango2-mea.REF.miyake.2023.100352">Miyake et al 2023</a>].</p><p><b>Cardiac crisis</b> is defined by the development of ventricular arrhythmias, cardiomyopathy (heart failure), or cardiac arrest during an acute metabolic crisis. Cardiac crisis only occurs during metabolic crisis, affecting 65% of all individuals with acute metabolic crises in the natural history study [<a class="bk_pop" href="#tango2-mea.REF.miyake.2023.100352">Miyake et al 2023</a>].</p><p>During cardiac crisis, life-threatening recalcitrant ventricular tachycardia (VT) or torsade de pointes can occur, leading to hemodynamic instability and cardiac arrest. These events can occur when an individual is acutely ill but also in those who appear stable with improving CK levels. The presence of marked QTc prolongation, type I Brugada pattern, and ventricular ectopy are concerning, as they precede VT (QTc >500 msec is associated with an increased risk of torsade de pointes). VT is difficult to control, often unresponsive to typical anti-arrhythmic therapy, and once VT occurs it may result in cardiac arrest and death. Cardiac arrest has been reported in almost 75% of individuals in cardiac crisis.</p><p>Ventricular arrhythmias and unexplained cardiovascular collapse during crises are the leading causes of mortality. Unexplained sudden death during sleep not associated with metabolic crisis has also been reported [<a class="bk_pop" href="#tango2-mea.REF.hoebeke.2021.80">Hoebeke et al 2021</a>, <a class="bk_pop" href="#tango2-mea.REF.miyake.2022.1673">Miyake et al 2022</a>].</p><p>Affected individuals can also demonstrate echocardiographic changes during metabolic crisis, including ventricular dilatation and heart failure (systolic dysfunction). About 70% of those in cardiac crisis can develop heart failure. Systolic dysfunction can develop rapidly, and systolic function should be monitored closely during crisis. Both arrhythmias and cardiomyopathy are reversible, and full recovery is possible if the crisis resolves [<a class="bk_pop" href="#tango2-mea.REF.miyake.2022.1673">Miyake et al 2022</a>]. Heart failure (systolic dysfunction) has not yet been reported in individuals who are not experiencing a cardiac crisis; however, heart transplantation has been performed in one individual, and long-term cardiac follow up among all affected individuals is lacking [<a class="bk_pop" href="#tango2-mea.REF.meisner.2020.e002928">Meisner et al 2020</a>].</p><p>Supraventricular tachycardias and heart block have also been rarely reported.</p><p><b>Seizures</b> are observed outside the periods of crisis in approximately 40%-50% of individuals [<a class="bk_pop" href="#tango2-mea.REF.schymick.2022.473">Schymick et al 2022</a>, <a class="bk_pop" href="#tango2-mea.REF.miyake.2023.100352">Miyake et al 2023</a>]. A variety of seizure types have been reported, including myoclonic and tonic-clonic events. Other seizure types included generalized tonic, atonic, absence, and focal motor seizures. Infantile spasms have been reported in a few individuals. Seizures are generally responsive to anti-seizure medications, although about one third of affected individuals have drug-resistant epilepsy [<a class="bk_pop" href="#tango2-mea.REF.dines.2019.601">Dines et al 2019</a>, <a class="bk_pop" href="#tango2-mea.REF.miyake.2023.100352">Miyake et al 2023</a>].</p><p><b>Brain imaging abnormalities.</b> Prominent lateral ventricles and progressive brain atrophy on MRI examination have been reported in several affected individuals. While some older individuals have normal brain imaging studies, generalized cerebral atrophy has been described even in young infants with early disease presentation. Microcephaly has been seen in about 20% of affected individuals.</p><p><b>Hypothyroidism</b>. Elevated serum thyroid-stimulating hormone (TSH) with low or low-normal free thyroxine are seen, consistent with primary hypothyroidism. Affected individuals are typically diagnosed with hypothyroidism during acute crises with evaluation for muscle weakness or altered mental status. Hypothyroidism has also been identified in individuals without a history of metabolic crisis.</p><p><b>Ophthalmologic manifestations.</b> Intermittent exotropia has been observed in affected individuals and appears to worsen with fatigue, illness, TANGO2 spells, and metabolic crises. Rarely, optic atrophy has been identified.</p><p><b>Gastrointestinal concerns.</b> Constipation is common and affects approximately 50% of individuals. TANGO2 spell manifestations are more common when constipation is more severe. Dysphagia and episodic worsening of swallow function have been observed during TANGO2 spells and metabolic crises, increasing the risk of aspiration due to inability to manage secretions and liquids. Delayed gastric emptying with gastrointestinal dysmotility have also been reported during crises. Some individuals require gastrostomy tube feeding, particularly if maintaining feedings is difficult during times of illness and even at baseline [<a class="bk_pop" href="#tango2-mea.REF.dines.2019.601">Dines et al 2019</a>, <a class="bk_pop" href="#tango2-mea.REF.miyake.2022.1673">Miyake et al 2022</a>].</p><p><b>Hearing loss.</b> Sensorineural hearing loss has been described in rare instances.</p></div><div id="tango2-mea.GenotypePhenotype_Correlation"><h3>Genotype-Phenotype Correlations</h3><p>To date, no clear <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> have been reported.</p></div><div id="tango2-mea.Nomenclature"><h3>Nomenclature</h3><p>TANGO2 deficiency is also referred to as "metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration" (MECRCN) in OMIM.</p></div><div id="tango2-mea.Prevalence"><h3>Prevalence</h3><p>The worldwide prevalence of TANGO2 deficiency is estimated to be 1:1,000,000, likely affecting more than 8,000 individuals.</p><p><i>TANGO2</i> pathogenic variants that are reported to be more common include a ~34-kb <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> encompassing exons 3-9; this is the most common <a class="def" href="/books/n/gene/glossary/def-item/allele/">allele</a> observed, with an approximate <a class="def" href="/books/n/gene/glossary/def-item/allele-frequency/">allele frequency</a> of 0.14% in the non-Finnish/European population. The minor allele frequency of another recurrent variant, c.460G>A (p.Gly154Arg), is reported to be 0.07% in the Latino/admixed American population in gnomAD.</p></div></div><div id="tango2-mea.Genetically_Related_Allelic_D"><h2 id="_tango2-mea_Genetically_Related_Allelic_D_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in <i>TANGO2</i>.</p><p><a href="/books/n/gene/gr_22q11deletion/"><b>22q11.2 deletion syndrome</b></a><b>.</b> 22q11.2 deletions encompass multiple genes, typically including <i>TANGO2</i>. Individuals with 22q11.2 <a class="def" href="/books/n/gene/glossary/def-item/deletion-syndrome/">deletion syndrome</a> who have a second genetic alteration involving <i>TANGO2</i> in <a class="def" href="/books/n/gene/glossary/def-item/trans/"><i>trans</i></a> with the 22q11.2 deletion will have features of both 22q11.2 deletion syndrome and TANGO2 deficiency.</p></div><div id="tango2-mea.Differential_Diagnosis"><h2 id="_tango2-mea_Differential_Diagnosis_">Differential Diagnosis</h2><div id="tango2-mea.T.genetic_disorders_to_consid" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genetic Disorders to Consider in the Differential Diagnosis of TANGO2 Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.T.genetic_disorders_to_consid/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.T.genetic_disorders_to_consid_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Features Overlapping w/TANGO2 Deficiency</th><th id="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Features Distinguishing from TANGO2 Deficiency</th></tr></thead><tbody><tr><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ACADVL</i>
|
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</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/vlcad/">Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency</a>
|
||
</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Arrhythmias, rhabdomyolysis, intermittent hypoglycemia</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In VLCAD deficiency: hypoketotic hypoglycemia, hepatomegaly</td></tr><tr><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>CPT2</i>
|
||
</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/cpt2/">Carnitine palmitoyltransferase II (CPT II) deficiency</a>
|
||
</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Muscle weakness during attacks, myoglobinuria, cardiac arrhythmias, seizures, coma after infection or prolonged fasting</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In CPT II deficiency: liver failure, hypoketotic hypoglycemia</td></tr><tr><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>HADHA</i>
|
||
<br />
|
||
<i>HADHB</i>
|
||
</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/lchad/">Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) / trifunctional protein deficiency (TFP)</a>
|
||
</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">↑ CK, prolonged QTc, & cardiomyopathy</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In LCHAD/TFP deficiency: hypoketotic hypoglycemia, pigmentary retinopathy, peripheral neuropathy</td></tr><tr><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<p>
|
||
<i>LPIN1</i>
|
||
</p>
|
||
</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<p><i>LPIN1</i>-related acute recurrent myoglobinuria (OMIM <a href="https://omim.org/entry/268200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">268200</a>)</p>
|
||
</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Muscle weakness, acute recurrent rhabdomyolysis, myoglobinuria</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In <i>LPIN1</i>-related acute recurrent myoglobinuria: absence of seizures & cardiac arrhythmias</td></tr><tr><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>PYGM</i>
|
||
</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/gsd5/">Glycogen storage disease type V</a> (GSDV, McArdle disease) & other defects of glucose/glycogen metabolism</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Recurrent rhabdomyolysis, myoglobinuria</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In GSDV: presence of muscle cramps & absence of seizures & cardiac arrhythmias</td></tr><tr><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<p>
|
||
<i>SLC25A20</i>
|
||
</p>
|
||
</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<p>
|
||
<a href="/books/n/gene/cact-def/">Carnitine-acylcarnitine translocase (CACT) deficiency</a>
|
||
</p>
|
||
</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ventricular tachycardia, cardiomyopathy, rhabdomyolysis, hyperammonemia, abnormal liver enzymes, ↑ long chain acylcarnitines</td><td headers="hd_h_tango2-mea.T.genetic_disorders_to_consid_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In CACT deficiency: presence (typically) of ↑ C16 & C18 (although C14:1 can also be ↑) & absence of prolonged QTc interval</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; CK = creatine phosphokinase; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; QTc = corrected QT</p></div></dd></dl></div></div></div><p><b>Mitochondrial disorders.</b> Lactic acidosis, myopathy, and seizures are seen in a wide variety of mitochondrial disorders (see <a href="/books/n/gene/mt-overview/">Primary Mitochondrial Disorders Overview</a>). However, unlike TANGO2 deficiency, mitochondrial disorders are rarely associated with ventricular tachycardia in the setting of acute metabolic crisis with elevated creatine phosphokinase.</p></div><div id="tango2-mea.Management"><h2 id="_tango2-mea_Management_">Management</h2><p>No clinical practice guidelines for TANGO2 deficiency have been published.</p><div id="tango2-mea.Evaluations_Following_Initial"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with TANGO2 deficiency in <b>acute metabolic crisis</b>, the evaluations summarized in <a href="/books/NBK476443/table/tango2-mea.T.recommended_evaluations_fol/?report=objectonly" target="object" rid-ob="figobtango2meaTrecommendedevaluationsfol">Table 4a</a> are recommended.</p><p>To establish the extent of disease and needs in all other individuals diagnosed with TANGO2 deficiency, the evaluations summarized in <a href="/books/NBK476443/table/tango2-mea.T.recommended_evaluations_fol_1/?report=objectonly" target="object" rid-ob="figobtango2meaTrecommendedevaluationsfol1">Table 4b</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="tango2-mea.T.recommended_evaluations_fol" class="table"><h3><span class="label">Table 4a. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with TANGO2 Deficiency in Acute Metabolic Crisis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.T.recommended_evaluations_fol/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.T.recommended_evaluations_fol_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">System/Concern</th><th id="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Evaluation</th><th id="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>General</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For those w/new diagnosis in acute metabolic crisis, admit to ICU for observation</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic assessment of mental status, gait, strength</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Metabolic</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Blood glucose, CK, ALT, AST</div></li><li class="half_rhythm"><div>Chemistry panel incl serum Mg</div></li><li class="half_rhythm"><div>Plasma lactate & troponin</div></li><li class="half_rhythm"><div>Global MAPS™ if feasible</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Feeding/Nutrition</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess nutrition, swallowing, & ability for oral intake vs need for NGT, IV, TPN</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dysphagia can be episodic, w/↑ risk of aspiration due to inability to manage secretions & liquids.</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiovascular</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Continuous bedside rhythm monitoring should be initiated immediately & continued throughout hospitalization to assess for ventricular ectopy & life-threatening ventricular arrhythmias until crisis resolves.</div></li><li class="half_rhythm"><div>Obtain EKG to measure QTc & assess for Brugada pattern</div></li><li class="half_rhythm"><div>Echocardiogram to assess ventricular function</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Placement of monitoring leads in high precordial space can help identify Brugada pattern</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrine</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">TSH & free T4 to eval for hypothyroidism</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for constipation.</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ALT = alanine transaminase; AST = aspartate transaminase; CK = creatine phosphokinase; Global MAPS™ = Global Metabolomic Assisted Pathway Screen; ICU = intensive care unit; IV = intravenous; Mg = magnesium; NGT = nasogastric tube; QTc = corrected QT; T4 = thyroxine; TPN = total parenteral nutrition; TSH = thyroid-stimulating hormone</p></div></dd></dl></div></div></div><div id="tango2-mea.T.recommended_evaluations_fol_1" class="table"><h3><span class="label">Table 4b. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with TANGO2 Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.T.recommended_evaluations_fol_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.T.recommended_evaluations_fol_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<p>Developmental assessment</p>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl motor, adaptive, cognitive, & speech-language eval</div></li><li class="half_rhythm"><div>Eval for early intervention / special education</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Referral to neurologist if seizures are suspected or spasticity is present</div></li><li class="half_rhythm"><div>EEG if seizures are suspected</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Feeding/Nutrition</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess nutritional status incl vitamin B intake</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiovascular</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Referral to cardiac electrophysiologist or cardiologist (if electrophysiologist is not available)</div></li><li class="half_rhythm"><div>EKG & Holter</div></li><li class="half_rhythm"><div>Echocardiogram</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To establish baseline EKG, rhythm, & cardiac function</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrine</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">TSH, free T4</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To eval for hypothyroidism</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ophthalmologic</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic exam</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To eval for strabismus & optic atrophy</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for constipation.</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Audiologic</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic eval</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic counseling</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of TANGO2 deficiency to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support</b>
|
||
<br />
|
||
<b>& resources</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
|
||
<ul><li class="half_rhythm"><div>Community or <a href="#tango2-mea.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a>;</div></li><li class="half_rhythm"><div>Social work involvement for parental support;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul>
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</td><td headers="hd_h_tango2-mea.T.recommended_evaluations_fol_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; T4 = thyroxine; TSH = thyroid-stimulating hormone</p></div></dd><dt>1. </dt><dd><div id="tango2-mea.TF.4b.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="tango2-mea.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>There is no cure for TANGO2 deficiency.</p><div id="tango2-mea.Targeted_Therapy"><h4>Targeted Therapy</h4><p>
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<i>In GeneReviews, a targeted therapy is one that addresses the specific underlying mechanism of disease causation (regardless of whether the therapy is significantly efficacious for one or more manifestation of the genetic condition); would otherwise not be considered without knowledge of the underlying genetic cause of the condition; or could lead to a cure</i>. —ED</p><p>Daily supplementation with a multivitamin including all eight B vitamins or a B-complex vitamin at the minimum recommended daily allowance for age (see <a href="/books/NBK476443/table/tango2-mea.T.minimum_recommended_daily_a/?report=objectonly" target="object" rid-ob="figobtango2meaTminimumrecommendeddailya">Table 5</a>) has been show to significantly reduce the development of metabolic crises and arryhythmias in individuals with TANGO2 deficiency [<a class="bk_pop" href="#tango2-mea.REF.miyake.2023.100352">Miyake et al 2023</a>, <a class="bk_pop" href="#tango2-mea.REF.sandkuhler.2023.161">Sandkuhler et al 2023</a>].</p><ul><li class="half_rhythm"><div>B-complex vitamins include thiamine (B<sub>1</sub>), riboflavin (B<sub>2</sub>), niacin (B<sub>3</sub>), pantothenic acid (B<sub>5</sub>), pyridoxine (B<sub>6</sub>), biotin (B<sub>7</sub>), folate (B<sub>9</sub>), and cyanocobalamin (B<sub>12</sub>).</div></li><li class="half_rhythm"><div>The exact dose of B vitamin supplementation required to prevent crises is not known.</div></li><li class="half_rhythm"><div>B vitamins are water soluble with no known side effects, with the exception of high doses of vitamin B<sub>6</sub>, which can lead to peripheral neuropathy.</div></li></ul><div id="tango2-mea.T.minimum_recommended_daily_a" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Minimum Recommended Daily Allowance for B Vitamins by Age and Sex</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.T.minimum_recommended_daily_a/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.T.minimum_recommended_daily_a_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_1" rowspan="3" scope="col" colspan="1" headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_1" style="text-align:left;vertical-align:middle;">Vitamin</th><th id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_2" rowspan="3" scope="col" colspan="1" headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_2" style="text-align:left;vertical-align:middle;">Units</th><th id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3" colspan="9" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Recommended Daily Allowance by Age & Sex <sup>1</sup></th></tr><tr><th headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_1" id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_1" rowspan="2" colspan="1" scope="colgroup" style="text-align:left;vertical-align:middle;">0-6 mos</th><th headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_2" id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_2" rowspan="2" scope="col" colspan="1" style="text-align:left;vertical-align:middle;">7-12 mos</th><th headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_3" id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_3" rowspan="2" scope="col" colspan="1" style="text-align:left;vertical-align:middle;">1-3 yrs</th><th headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_4" id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_4" rowspan="2" scope="col" colspan="1" style="text-align:left;vertical-align:middle;">4-8 yrs</th><th headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_5" id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_5" rowspan="2" scope="col" colspan="1" style="text-align:left;vertical-align:middle;">9-13 yrs</th><th headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3" id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">14-18 yrs</th><th headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3" id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">>18 yrs</th></tr><tr><th headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6" id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Male</th><th headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6" id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Female</th><th headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7" id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Male</th><th headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7" id="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Female</th></tr></thead><tbody><tr><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">B<sub>1</sub></td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">mg</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.2</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.3</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.5</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.6</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.9</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.2</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.2</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.1</td></tr><tr><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">B<sub>2</sub></td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">mg</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.3</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.4</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.5</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.6</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.9</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.3</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.3</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.1</td></tr><tr><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">B<sub>3</sub></td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">mg</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">14</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">14</td></tr><tr><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">B<sub>5</sub></td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">mg</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.7</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.8</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5</td></tr><tr><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">B<sub>6</sub></td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">mg</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.1</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.3</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.5</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.6</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.3</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.2</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.3</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.3</td></tr><tr><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">B<sub>7</sub></td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">µg</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30</td></tr><tr><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">B<sub>9</sub></td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">µg</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">65</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">80</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">150</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">200</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">300</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">400</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">400</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">400</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">400</td></tr><tr><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">B<sub>12</sub></td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">µg</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.4</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.5</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.9</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.2</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.8</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2.4</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_6 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2.4</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2.4</td><td headers="hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_1_3 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_2_7 hd_h_tango2-mea.T.minimum_recommended_daily_a_1_1_3_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2.4</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="tango2-mea.TF.5.1"><p class="no_margin">Adapted from <a href="https://www.hc-sc.gc.ca/fn-an/alt_formats/hpfb-dgpsa/pdf/nutrition/dri_tables-eng.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Dietary Reference Intakes</a> (pdf)</p></div></dd></dl></div></div></div></div><div id="tango2-mea.Supportive_Care"><h4>Supportive Care</h4><p>Early management during acute metabolic crises is paramount to prevent the development of a cardiac crisis. A plan for emergency treatment should be in place for families and physicians to initiate appropriate steps to suppress acute catabolism and promote hydration to minimize the risk of life-threatening rhabdomyolysis and cardiac tachyarrhythmias (see <a href="/books/NBK476443/table/tango2-mea.T.treatment_for_acute_metabol/?report=objectonly" target="object" rid-ob="figobtango2meaTtreatmentforacutemetabol">Table 6a</a>).</p><p>Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see <a href="/books/NBK476443/table/tango2-mea.T.routine_nonacute_treatment/?report=objectonly" target="object" rid-ob="figobtango2meaTroutinenonacutetreatment">Table 6b</a>).</p><div id="tango2-mea.T.treatment_for_acute_metabol" class="table"><h3><span class="label">Table 6a. </span></h3><div class="caption"><p>Treatment for Acute Metabolic Crises in Individuals with TANGO2 Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.T.treatment_for_acute_metabol/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.T.treatment_for_acute_metabol_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration/Other</th></tr></thead><tbody><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>General</b>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>Admit to floor unit for observation/</b><br /><b>mgmt if:</b>
|
||
<ul><li class="half_rhythm"><div>Well appearing;</div></li><li class="half_rhythm"><div>Eating regular diet;</div></li><li class="half_rhythm"><div>Normal glucose levels on admission;</div></li><li class="half_rhythm"><div>EKG QTc <480 msec.</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for episodic dysphagia & risk of aspiration.</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"><p><b>Admit to ICU if:</b></p>
|
||
<ul><li class="half_rhythm"><div>New diagnosis;</div></li><li class="half_rhythm"><div>Ill appearing or obtunded;</div></li><li class="half_rhythm"><div>Not tolerating oral diet;</div></li><li class="half_rhythm"><div>Hypoglycemia;</div></li><li class="half_rhythm"><div>EKG QTc ≥480 msec.</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hypoglycemia/</b>
|
||
<br />
|
||
<b>Dehydration</b>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>IV fluids w/dextrose</div></li><li class="half_rhythm"><div>Echocardiogram to assess cardiac function</div></li><li class="half_rhythm"><div>Adjust IV fluid rate to avoid pulmonary edema; if normal cardiac function, IV fluids at 1.5-2x maintenance rate</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Persistent hypoglycemia is not common when nutritional support is initiated.</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Electrolyte derangements</b>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Treat as necessary to maintain normal potassium.</div></li><li class="half_rhythm"><div>Maintain serum Mg >2.2 mg/dL w/oral or IV Mg supplements.</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Persistent electrolyte derangements are not common.</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Rhabdomyolysis</b>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor CK daily during acute crisis until consistent downward trend, then monitor CK intermittently.</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Vitamin supplementation is critical, especially folate (vitamin B<sub>9</sub>) & pantothenic acid (vitamin B<sub>5</sub>).</div></li><li class="half_rhythm"><div>Administer vitamins via NGT, IV, or TPN if not tolerating PO.</div></li><li class="half_rhythm"><div>IV fluids w/dextrose alone will not reverse rhabdomyolysis; nutritional support has been shown to ↓ CK levels.</div></li><li class="half_rhythm"><div>Acute kidney injury & complications from rhabdomyolysis are rare.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac mgmt/monitoring</b>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Obtain EKG to assess QTc & presence of Brugada pattern. Daily EKG to monitor QTc & assess for presence of Brugada pattern. Continue daily EKG until steady downward trend in serum CK; if QTc becomes >480 msec, transfer to ICU.</div></li><li class="half_rhythm"><div>IV Mg supplementation to maintain serum Mg >2.2 mg/dL. If QTc is <480 msec, then maintain Mg levels >2.2 mg/dL using oral or intermittent IV supplements. If QTc is >480 msec, then replace Mg using continuous IV.</div></li><li class="half_rhythm"><div>Continuous rhythm monitoring to assess for PVCs & arrhythmias, particularly VT. Transfer to ICU if any premature ventricular contractions are noted.</div></li><li class="half_rhythm"><div>Obtain echocardiogram to assess function & adjust IVF rate based on cardiac function. Repeat echocardiogram every 3 days; echocardiogram less frequently after downward trend in serum CK; echocardiogram prior to discharge.</div></li><li class="half_rhythm"><div>Multivitamin supplementation upon admission incl all 8 B vitamins (minimum RDA for age); can be given in IV fluids until oral assessment completed.</div></li><li class="half_rhythm"><div>Monitor oral intake. Nutritional support (oral, NGT, or TPN) can prevent evolving cardiac crisis; most sick persons do not consume enough by oral diet.</div></li><li class="half_rhythm"><div>Ensure access to ICU w/ECMO in case of recalcitrant arrhythmia.</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Use of continuous monitoring leads in the high precordial placement can be helpful to visualize the intermittent development of a type I Brugada pattern.</div></li><li class="half_rhythm"><div>Avoid QT-prolonging drugs.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac arrhythmias <sup>1</sup></b>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>If Brugada pattern is present on EKG:</b> Monitor in ICU.</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Avoid sodium channel blockers (e.g., lidocaine, procainamide, amiodarone).</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><b>In those w/PVCs:</b>
|
||
<ul><li class="half_rhythm"><div>Immediate transfer to ICU</div></li><li class="half_rhythm"><div>Continuous IV Mg to maintain serum Mg >2.2 mg/dL</div></li><li class="half_rhythm"><div>Keep isoproterenol bolus (0.03-0.05 µg/kg) at bedside.</div></li><li class="half_rhythm"><div>Consider isoproterenol infusion at 0.01-1 µg/kg/min. Titrate to maintain heart rates that suppress ectopy.</div></li><li class="half_rhythm"><div>IV multivitamin supplement incl all 8 B vitamins</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>PVCs are harbingers of VT, which can develop rapidly once PVCs are noted.</div></li><li class="half_rhythm"><div>Beta-adrenergic blockers have not been shown to be consistently effective. VT tends to occur at lower heart rates, & hence avoiding beta-adrenergic blockers should be strongly considered.</div></li><li class="half_rhythm"><div>Avoid QT-prolonging drugs during crisis.</div></li><li class="half_rhythm"><div>Avoid sodium channel blockers (e.g., lidocaine, procainamide, amiodarone)</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><b>In those w/VT or TdPs & hemodynamic instability:</b>
|
||
<ul><li class="half_rhythm"><div>Continuous bedside rhythm monitoring</div></li><li class="half_rhythm"><div>Direct current cardioversion is acutely effective, but VT/VF is often recurrent & recalcitrant.</div></li><li class="half_rhythm"><div>Administer isoproterenol bolus (0.03-0.05 µg/kg) & repeat if necessary.</div></li><li class="half_rhythm"><div>Continuous isoproterenol infusion at 0.01-1 µg/kg/min. Titrate to maintain heart rates that suppress ectopy. VT tends to occur more frequently at lower heart rates.</div></li><li class="half_rhythm"><div>IV multivitamin supplement incl all 8 B vitamins.</div></li><li class="half_rhythm"><div>Consider 1 g IV folate (B<sub>9</sub>).</div></li><li class="half_rhythm"><div>In those w/ICD w/atrial lead, use atrial pacing at rates faster than sinus. Be cautious of development of tachycardia-induced cardiomyopathy.</div></li><li class="half_rhythm"><div>If TdPs continues despite first-line approaches, consider pacing using temporary esophageal pacing lead or ventricular lead.</div></li><li class="half_rhythm"><div>If VT/TdPs is recalcitrant, have ECMO treatment available.</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Temporary or surgical sympathetic denervation can be considered for recalcitrant VT.</div></li><li class="half_rhythm"><div>Consider IV calcium channel blocker.</div></li><li class="half_rhythm"><div>Consider avoiding beta-adrenergic blockers.</div></li><li class="half_rhythm"><div>Avoid sodium channel blockers (e.g., lidocaine, procainamide, amiodarone).</div></li><li class="half_rhythm"><div>VT is extremely difficult to manage in persons w/TANGO2 deficiency. VT is often unresponsive to standard therapies; in addition, standard therapies can make VT worse.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><b>For</b>
|
||
<b>uncontrollable, hemodynamically unstable VT:</b> In addition to treatments for cardiac arrythmias, direct current cardioversion, acute pacing, & consideration of ECMO support</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Backup support (e.g., ECMO) needs to be available, as medications for VT may potentiate or worsen arrhythmias.</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac dysfunction/</b>
|
||
<br />
|
||
<b>cardiomyopathy</b>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>If systolic function is mildly depressed:</b>
|
||
<ul><li class="half_rhythm"><div>Continue monitoring.</div></li><li class="half_rhythm"><div>Continue nutritional support & vitamin supplementation.</div></li><li class="half_rhythm"><div>Maintain Mg >2.2 mg/dL.</div></li><li class="half_rhythm"><div>Consider inotropic support that ↑ heart rate (see treatments for <b>mildly to moderately depressed systolic function</b> next)</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><b>If systolic function is mildly to moderately depressed:</b>
|
||
<ul><li class="half_rhythm"><div>Isoproterenol can be given, but use w/caution for extended periods & monitor cardiac function closely.</div></li><li class="half_rhythm"><div>Atrial pacing can be used as an alternative to isoproterenol. <sup>2</sup></div></li><li class="half_rhythm"><div>If inotropic support is required, one that ↑ heart rate such as epinephrine should be considered, as this may help minimize VT/TdPs</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Atrial pacing is preferred over ventricular pacing.</div></li><li class="half_rhythm"><div>A transesophageal lead can be used in an emergency or for short-term pacing until a temporary wire can be placed.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><b>If systolic function is moderately to severely depressed:</b>
|
||
<ul><li class="half_rhythm"><div>Consider inotropic support that ↑ heart rate (epinephrine), which may potentially prevent arrhythmias. Be careful w/fluid resuscitation to avoid pulmonary edema.</div></li><li class="half_rhythm"><div>Consider ECMO, since full recovery has been shown when metabolic crisis resolves.</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Systolic dysfunction can develop rapidly.</div></li><li class="half_rhythm"><div>Pulseless electrical activity & cardiac shock leading to death have occurred despite treatment.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"><b>If systolic function is severely depressed:</b>
|
||
<ul><li class="half_rhythm"><div>Continue Mg as first-line treatment.</div></li><li class="half_rhythm"><div>Consider inotropic support that ↑ heart rate (epinephrine).</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hypothyroidism</b>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Levothyroxine treatment</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Constipation /</b>
|
||
<br />
|
||
<b>GI dysmotility</b>
|
||
</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatments for constipation & ↓ gut motility</td><td headers="hd_h_tango2-mea.T.treatment_for_acute_metabol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">CK = creatine phosphokinase; ECMO = extracorporeal membrane oxygenation; GI = gastrointestinal; ICD = implantable cardioverter defibrillator; ICU = intensive care unit; IV = intravenous; Mg = magnesium; NGT = nasogastric tube; PO = per os (by mouth); PVC = premature ventricular contraction; RDA = recommended daily allowance; TdPs = torsade de pointes; TPN = total parenteral nutrition; VF = ventricular fibrillation; VT = ventricular tachycardia</p></div></dd><dt>1. </dt><dd><div id="tango2-mea.TF.6a.1"><p class="no_margin">Cardiac rhythmic disturbances that occur in individuals with TANGO2 deficiency are predominantly ventricular tachyarrhythmias.</p></div></dd><dt>2. </dt><dd><div id="tango2-mea.TF.6a.2"><p class="no_margin">This can be done with a temporary pacing wire for longer-term pacing.</p></div></dd></dl></div></div></div><div id="tango2-mea.T.routine_nonacute_treatment" class="table"><h3><span class="label">Table 6b. </span></h3><div class="caption"><p>Routine (Non-Acute) Treatment in Individuals with TANGO2 Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.T.routine_nonacute_treatment/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.T.routine_nonacute_treatment_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration/Other</th></tr></thead><tbody><tr><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Developmental delay /</b>
|
||
<br />
|
||
<b>Intellectual disability</b>
|
||
</td><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#tango2-mea.Developmental_Delay__Intellec">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>History of cardiac arrhythmias / cardiomyopathy <sup>1</sup></b>
|
||
</td><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Data suggest that nutritional support w/daily supplemental B vitamins prevents crises & arrhythmias & thus ICDs may not be necessary. However, some persons w/documented ventricular arrhythmias have undergone placement of an automated ICD.</td><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Avoid beta-adrenergic blockers.</td></tr><tr><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Seizures</b>
|
||
</td><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment w/ASM</td><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Consider referral to neurologist.</div></li><li class="half_rhythm"><div>Avoid ketogenic diet; acute metabolic crises after initiation of ketogenic diet have been reported.</div></li><li class="half_rhythm"><div>Valproate has been safely & successfully used.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hypothyroidism</b>
|
||
</td><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Levothyroxine</td><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider referral to endocrinologist.</td></tr><tr><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal/Nutrition</b>
|
||
</td><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per gastroenterologist / nutritionist / feeding team:
|
||
<ul><li class="half_rhythm"><div>Feeding therapy as needed</div></li><li class="half_rhythm"><div>Gastrostomy tube feeding as needed</div></li><li class="half_rhythm"><div>Standard treatments for constipation</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.routine_nonacute_treatment_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Consider gastrostomy tube in persons w/issues maintaining adequate nutritional intake to ensure adequate nutrition & vitamin intake during times of illness.</div></li><li class="half_rhythm"><div>No restriction in diet is required. Frequent snacking is typically reported.</div></li><li class="half_rhythm"><div>Avoid fasting.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ASM = anti-seizure medication; ICD = implantable cardioverter defibrillator</p></div></dd><dt>1. </dt><dd><div id="tango2-mea.TF.6b.1"><p class="no_margin">Questions regarding definitive treatment remain.</p></div></dd></dl></div></div></div><div id="tango2-mea.Developmental_Delay__Intellec"><h5>
|
||
<b>Developmental Delay / Intellectual Disability Management Issues</b>
|
||
</h5><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the US; standard recommendations may vary from country to country. In individuals with TANGO2 deficiency, receptive language skills are generally better than expressive language skills, and this should be taken into account during assessments.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div>IEP services:</div><ul><li class="half_rhythm"><div>An IEP provides specially designed instruction and related services to children who qualify.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine whether any changes are needed.</div></li><li class="half_rhythm"><div>Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.</div></li><li class="half_rhythm"><div>Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.</div></li><li class="half_rhythm"><div>PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</div></li><li class="half_rhythm"><div>As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.</div></li></ul></li><li class="half_rhythm"><div>A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.</div></li><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div><div id="tango2-mea.Motor_Dysfunction"><h5>
|
||
<b>Motor Dysfunction</b>
|
||
</h5><p>
|
||
<b>Gross motor dysfunction</b>
|
||
</p><ul><li class="half_rhythm"><div>Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset complications.</div></li><li class="half_rhythm"><div>Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</div></li><li class="half_rhythm"><div>For muscle tone abnormalities including hypertonia, consider involving appropriate specialists to aid in management of baclofen, Botox<sup>®</sup>, or orthopedic procedures.</div></li></ul><p><b>Fine motor dysfunction.</b> Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.</p><p><b>Oral motor dysfunction.</b> Assuming that the individual can safely eat by mouth, feeding therapy – typically from an occupational or speech therapist – is recommended for affected individuals who have difficulty feeding. During metabolic crisis, swallowing function can be compromised and aspiration may be at risk. Evaluation should be considered to ensure safe feeding.</p><p><b>Communication issues.</b> Consider evaluation for alternative means of communication (e.g., <a href="https://www.asha.org/NJC/AAC/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">augmentative and alternative communication</a> [AAC]) for individuals who have significant expressive language difficulties.</p></div></div></div><div id="tango2-mea.Surveillance"><h3>Surveillance</h3><div id="tango2-mea.T.recommended_surveillance_fo" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with TANGO2 Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.T.recommended_surveillance_fo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.T.recommended_surveillance_fo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurodevelopment</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Physical medicine, OT/PT assessment of mobility, spasticity, self-help skills</div></li><li class="half_rhythm"><div>Monitor developmental progress & educational needs.</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Nutrition</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess vitamin B complex intake.</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consider measurement of vitamin B<sub>6</sub> serum level in those on high doses of B vitamins, as vitamin B<sub>6</sub> toxicity can lead to peripheral neuropathy.</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>For those w/prior metabolic crises:</b>
|
||
<ul><li class="half_rhythm"><div>EKG & Holter</div></li><li class="half_rhythm"><div>Echocardiogram</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually for first few yrs & then every 3 yrs or as recommended by cardiologist</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><b>For those w/o history of metabolic crisis</b>:
|
||
<ul><li class="half_rhythm"><div>EKG (baseline)</div></li><li class="half_rhythm"><div>Echocardiogram (baseline)</div></li></ul>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 3-5 yrs or as recommended by cardiologist</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor those w/seizures as clinically indicated.</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrine</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">TSH & free T4</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or per endocrinologist</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Eyes</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per ophthalmologist</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterologist / nutritionist / feeding team eval to assess feeding & nutritional status & for dysmotility</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per gastroenterologist & nutritionist</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for sensorineural hearing loss.</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/Community</b>
|
||
</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assess family need for care coordination, social work support (e.g., home nursing, local resources, palliative/respite care), or follow-up <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> if new questions arise (e.g., family planning).</td><td headers="hd_h_tango2-mea.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">OT = occupational therapy; PT = physical therapy; T4 = thyroxine; TSH = thyroid-stimulating hormone</p></div></dd></dl></div></div></div></div><div id="tango2-mea.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Avoid triggers for TANGO2 spells and acute metabolic crisis (e.g., fasting, dehydration, overexertion, exposure to excessive heat, ketogenic diet, infections).</p></div><div id="tango2-mea.Evaluation_of_Relatives_at_Ri"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to clarify the genetic status of apparently asymptomatic older and younger sibs of an affected individual by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> for the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> <i>TANGO2</i> pathogenic variants in order to identify as early as possible those who would benefit from prompt initiation of B-complex vitamin supplementation and recommended surveillance.</p><p>See <a href="#tango2-mea.Related_Genetic_Counseling_Is">Genetic Counseling</a> for issues related to testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="tango2-mea.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for information on clinical studies for a wide range of diseases and conditions. An international natural history study on TANGO2 deficiency is recruiting (<a href="https://clinicaltrials.gov/ct2/show/NCT05374616" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT05374616</a>).</p><p>Vitamin dosing and which specific vitamins help alleviate manifestations of TANGO2 deficiency are still under investigation.</p></div></div><div id="tango2-mea.Genetic_Counseling"><h2 id="_tango2-mea_Genetic_Counseling_">Genetic Counseling</h2><p>
|
||
<i>Genetic counseling is the process of providing individuals and families with
|
||
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
||
make informed medical and personal decisions. The following section deals with genetic
|
||
risk assessment and the use of family history and genetic testing to clarify genetic
|
||
status for family members; it is not meant to address all personal, cultural, or
|
||
ethical issues that may arise or to substitute for consultation with a genetics
|
||
professional</i>. —ED.</p><div id="tango2-mea.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>TANGO2 deficiency is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The parents of an affected child are presumed to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>TANGO2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> to confirm that both parents are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>TANGO2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> assessment.</div></li><li class="half_rhythm"><div>If a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> occurred as a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> event in the proband or as a <a class="def" href="/books/n/gene/glossary/def-item/postzygotic/">postzygotic</a> <i>de novo</i> event in a mosaic parent [<a class="bk_pop" href="#tango2-mea.REF.j_nsson.2017.519">Jónsson et al 2017</a>]. If the proband appears to have <a class="def" href="/books/n/gene/glossary/def-item/homozygous/">homozygous</a> pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:</div><ul><li class="half_rhythm"><div>A single- or multiexon <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> that was not detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> and that resulted in the artifactual appearance of homozygosity. (This is frequently observed in TANGO2 deficiency.)</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> with the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> that resulted in homozygosity for the pathogenic variant in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</div></li></ul></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and to date, are not known to be at risk of developing the disorder.</div></li></ul><p>
|
||
<b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>If both parents are known to be <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for a <i>TANGO2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a>, and a 25% chance of inheriting neither of the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pathogenic variants.</div></li><li class="half_rhythm"><div>Significant differences in clinical manifestations have been observed among sibs with the same <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>TANGO2</i> pathogenic variants [<a class="bk_pop" href="#tango2-mea.REF.schymick.2022.473">Schymick et al 2022</a>]. For the most part, younger sibs appear to be less affected; this may be related to earlier recognition of the disease and possibly early initiation of B-complex vitamin supplementation.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and to date, are not known to be at risk of developing the disorder.</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> To date, individuals with TANGO2 deficiency are not known to reproduce.</p><p><b>Other family members.</b> Each sib of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents is at a 50% risk of being a <a class="def" href="/books/n/gene/glossary/def-item/carrier/">carrier</a> of a <i>TANGO2</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="tango2-mea.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>TANGO2</i> pathogenic variants in the family.</p></div><div id="tango2-mea.Related_Genetic_Counseling_Is"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#tango2-mea.Evaluation_of_Relatives_at_Ri">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who are carriers or are at risk of being carriers.</div></li></ul></div><div id="tango2-mea.Prenatal_Testing_and_Preimpla"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>TANGO2</i> pathogenic variants have been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="tango2-mea.Resources"><h2 id="_tango2-mea_Resources_">Resources</h2><p>
|
||
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
||
support organizations and/or registries for the benefit of individuals with this disorder
|
||
and their families. GeneReviews is not responsible for the information provided by other
|
||
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>TANGO2 Research Foundation</b>
|
||
</div><div>300 Plaza Middlesex</div><div>Middletown CT 06457</div><div><b>Email:</b> info@tango2research.org</div><div>
|
||
<a href="https://tango2research.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.tango2research.org</a>
|
||
</div></li></ul>
|
||
</div><div id="tango2-mea.Molecular_Genetics"><h2 id="_tango2-mea_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div id="tango2-mea.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>TANGO2 Deficiency: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_tango2-mea.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_tango2-mea.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_tango2-mea.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_tango2-mea.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_tango2-mea.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_tango2-mea.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/128989" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>TANGO2</i>
|
||
</a>
|
||
</td><td headers="hd_b_tango2-mea.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=128989" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">22q11<wbr style="display:inline-block"></wbr>.21</a>
|
||
</td><td headers="hd_b_tango2-mea.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/Q6ICL3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Transport and Golgi organization protein 2 homolog</a>
|
||
</td><td headers="hd_b_tango2-mea.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=TANGO2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TANGO2</a>
|
||
</td><td headers="hd_b_tango2-mea.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=TANGO2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TANGO2</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="tango2-mea.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="tango2-mea.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for TANGO2 Deficiency (<a href="/omim/616830,616878" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/616830" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">616830</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TRANSPORT AND GOLGI ORGANIZATION 2 HOMOLOG; TANGO2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/616878" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">616878</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">METABOLIC CRISES, RECURRENT, WITH RHABDOMYOLYSIS, CARDIAC ARRHYTHMIAS, AND NEURODEGENERATION; MECRCN</td></tr></tbody></table></div></div><div id="tango2-mea.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>TANGO2</i> encodes for transport and Golgi organization protein 2 homolog (TANGO2) protein. The function of TANGO2 is not known. However, emerging studies suggest that TANGO2 deficiency likely causes perturbation in lipid biosynthesis and metabolism [<a class="bk_pop" href="#tango2-mea.REF.asadi.2023.358">Asadi et al 2023</a>]. TANGO2 deficiency appears to cause intrinsic metabolic defects that are exacerbated under stress conditions. Data also suggest that TANGO2 is required for ER-Golgi trafficking in cells [<a class="bk_pop" href="#tango2-mea.REF.milev.2021.426">Milev et al 2021</a>]. In the absence of TANGO2, there is a striking delay in transport of cargo proteins to the Golgi [<a class="bk_pop" href="#tango2-mea.REF.milev.2021.426">Milev et al 2021</a>].</p><p><b>Mechanism of disease causation.</b> Loss of function</p><div id="tango2-mea.T.notable_tango2_pathogenic_v" class="table"><h3><span class="label">Table 8. </span></h3><div class="caption"><p>Notable TANGO2 Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK476443/table/tango2-mea.T.notable_tango2_pathogenic_v/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__tango2-mea.T.notable_tango2_pathogenic_v_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_152906.7" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_152906<wbr style="display:inline-block"></wbr>.7</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_690870.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_690870<wbr style="display:inline-block"></wbr>.3</a>
|
||
</td><td headers="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.460G>A</td><td headers="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly154Arg</td><td headers="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common variant in persons of Hispanic ethnicity from Latin America [<a class="bk_pop" href="#tango2-mea.REF.lalani.2016.347">Lalani et al 2016</a>]</td></tr><tr><td headers="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NG_046857.1/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NG_046857<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~34-kb del<br />(incl exons 3-9)</td><td headers="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_tango2-mea.T.notable_tango2_pathogenic_v_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common variant in persons of European origin & persons of Hispanic ethnicity from Latin America [<a class="bk_pop" href="#tango2-mea.REF.lalani.2016.347">Lalani et al 2016</a>]</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></div></div></div></div></div><div id="tango2-mea.Chapter_Notes"><h2 id="_tango2-mea_Chapter_Notes_">Chapter Notes</h2><div id="tango2-mea.Author_Notes"><h3>Author Notes</h3><p>
|
||
<b>Author websites:</b>
|
||
</p><ul><li class="half_rhythm"><div>
|
||
<a href="https://www.bcm.edu/people/view/seema-lalani-m-d/b253d6f0-ffed-11e2-be68-080027880ca6" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Seema R Lalani, MD</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<a href="https://medicine.iu.edu/departments/genetics/faculty/38482/graham-brett/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Brett H Graham, MD, PhD</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<a href="https://www.bcm.edu/people/view/lindsay-burrage-m-d-ph-d/baylor-college-of-medicine-meet-our-team-physicians-a-l-genetics-clinics/b164351a-ffed-11e2-be68-080027880ca6/54d102e0-bdfc-4315-806f-3bf60a1612dc" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Lindsay Burrage, MD, PhD</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<a href="https://www.bcm.edu/people/view/fernando-scaglia-m-d/b17bf6de-ffed-11e2-be68-080027880ca6" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Fernando Scaglia, MD</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<a href="https://www.bcm.edu/people/view/claudia-soler-alfonso-m-d-f-a-c-m-g/488e837e-4a93-11e3-9de7-005056b104be" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Claudia Soler-Alfonso, MD</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<a href="https://www.texaschildrens.org/find-a-doctor/alfonso-hoyos-martinez-md-faap" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Alfonso Hoyos-Martinez, MD</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<a href="https://www.texaschildrens.org/profile/brandy-rawls-castillo-ms-rd-ld" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Brandy Rawls-Castillo, MS, RD, LD</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<a href="https://www.texaschildrens.org/find-a-doctor/kimberly-houck-md" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Kimberly Houck, MD</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<a href="https://www.texaschildrens.org/find-a-doctor/kevin-e-glinton-md-phd" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Kevin Glinton, MD, PhD</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<a href="https://www.bcm.edu/people/view/christina-miyake-m-d-m-s/b16d5031-ffed-11e2-be68-080027880ca6" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Christina Y Miyake, MD, MS</a>
|
||
</div></li></ul></div><div id="tango2-mea.Acknowledgments"><h3>Acknowledgments</h3><p>We thank the TANGO2 Research Foundation for their continued support.</p></div><div id="tango2-mea.Author_History"><h3>Author History</h3><p>Lindsay Burrage, MD, PhD (2018-present)<br />Kevin Glinton, MD, PhD (2023-present)<br />Brett Graham, MD, PhD (2018-present)<br />Kimberly Houck, MD (2023-present)<br />Alfonso Hoyos-Martinez, MD (2023-present)<br />Seema R Lalani, MD (2018-present)<br />Yi-Chen Lai, MD; Baylor College of Medicine (2018-2023)<br />Christina Y Miyake, MD, MS (2018-present)<br />Brandy Rawls-Castillo, MS, RD, LD (2023-present)<br />Fernando Scaglia, MD (2018-present)<br />Claudia Soler-Alfonso, MD (2018-present)<br />Yaping Yang, PhD (2018-present)</p></div><div id="tango2-mea.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>9 March 2023 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>20 December 2018 (ma) Comprehensive update posted live</div></li><li class="half_rhythm"><div>25 January 2018 (sw) Review posted live</div></li><li class="half_rhythm"><div>23 September 2017 (srl) Original submission</div></li></ul></div></div><div id="tango2-mea.References"><h2 id="_tango2-mea_References_">References</h2><div id="tango2-mea.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="tango2-mea.REF.asadi.2023.358">Asadi
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|
||
[<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tango2-mea.REF.sandkuhler.2023.161">Sandkuhler
|
||
SE, Zhang
|
||
L, Meisner
|
||
JK, Ghaloul-Gonzalez
|
||
L, Beach
|
||
CM, Harris
|
||
D, de Lonlay
|
||
P, Lalani
|
||
SR, Miyake
|
||
CY, Mackenzie
|
||
SJ. B-complex vitamins for patients with TANGO2-deficiency disorder.
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J Inherit Metab Dis.
|
||
2023;46:161-2.
|
||
[<a href="/pmc/articles/PMC10204720/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10204720</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36550018" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36550018</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="tango2-mea.REF.schymick.2022.473">Schymick
|
||
J, Leahy
|
||
P, Cowan
|
||
T, Ruzhnikov
|
||
MRZ, Gates
|
||
R, Fernandez
|
||
L, Pramanik
|
||
G; Undiagnosed Diseases Network, Yarlagadda V, Wheeler M, Bernstein JA, Enns GM, Lee C. Variable clinical severity in TANGO2 deficiency: case series and literature review.
|
||
Am J Med Genet A.
|
||
2022;188:473-487.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/34668327" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34668327</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Carnitine-Acylcarnitine Translocase Deficiency.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Carnitine-Acylcarnitine Translocase Deficiency.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Morales Corado JA, Lee CU, Enns GM. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301763" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" 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