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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2023/09/28">
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<meta name="citation_author" content="Ayman W El-Hattab">
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<meta name="citation_author" content="Fernando Scaglia">
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<meta name="citation_keywords" content="SUCLA2 Deficiency">
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<meta name="citation_keywords" content="SUCLA2 Deficiency">
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<meta name="citation_keywords" content="Succinate--CoA ligase [ADP-forming] subunit beta, mitochondrial">
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<meta name="citation_keywords" content="SUCLA2">
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<meta name="citation_keywords" content="SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria">
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<meta name="DC.Title" content="SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria">
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<meta name="DC.Contributor" content="Ayman W El-Hattab">
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<meta name="DC.Contributor" content="Fernando Scaglia">
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<meta name="description" content="SUCLA2-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (SUCLA2-related mtDNA depletion syndrome) is characterized by onset of the following features in infancy: developmental delay, hypotonia, dystonia, muscular atrophy, sensorineural hearing impairment, growth failure, and feeding difficulties. Other less frequent features include choreoathetosis, muscle weakness, recurrent vomiting, ptosis, and kyphoscoliosis. The median survival is age 20 years; approximately 30% of affected individuals succumb during childhood.">
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class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK6803_"><span class="title" itemprop="name"><i>SUCLA2</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: SUCLA2 Deficiency</div><p class="contribs">El-Hattab AW, Scaglia F.</p><p class="fm-aai"><a href="#_NBK6803_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 22 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="sucla2-def.Summary" itemprop="description"><h2 id="_sucla2-def_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>SUCLA2</i>-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (<i>SUCLA2</i>-related mtDNA depletion syndrome) is characterized by onset of the following features in infancy: developmental delay, hypotonia, dystonia, muscular atrophy, sensorineural hearing impairment, growth failure, and feeding difficulties. Other less frequent features include choreoathetosis, muscle weakness, recurrent vomiting, ptosis, and kyphoscoliosis. The median survival is age 20 years; approximately 30% of affected individuals succumb during childhood.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>SUCLA2</i>-related mtDNA depletion syndrome is established in a proband with suggestive findings and biallelic pathogenic variants in <i>SUCLA2</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Appropriate early developmental support; physical therapy to maintain muscle function and prevent joint contractures; antiseizure medication for epileptic seizures; hearing aids / cochlear implantation for sensorineural hearing loss; gastrostomy tube placement as needed to assure adequate caloric intake; blepharoplasty for significant ptosis; low vision services as needed; chest physiotherapy, aggressive antibiotic treatment of chest infections, and consideration of respiratory aids; bracing to treat scoliosis or kyphosis.</p><p><i>Surveillance:</i> Routine monitoring of development, growth, and hearing; periodic ophthalmologic evaluations; routine skeletal evaluations for kyphoscoliosis and joint contractures.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>SUCLA2</i>-related mtDNA depletion syndrome is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a <i>SUCLA2</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the <i>SUCLA2</i> pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing for <i>SUCLA2</i>-related mtDNA depletion syndrome are possible.</p></div></div><div id="sucla2-def.Diagnosis"><h2 id="_sucla2-def_Diagnosis_">Diagnosis</h2><p>No consensus clinical diagnostic criteria for <i>SUCLA2</i>-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (<i>SUCLA2</i>-related mtDNA depletion syndrome) have been published.</p><div id="sucla2-def.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>SUCLA2</i>-related mtDNA depletion syndrome typically manifests during early infancy and <b>should be suspected</b> in a proband with a combination of the following clinical, brain MRI, and supportive laboratory findings and family history.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div><b>Developmental delay (DD) / intellectual disability (ID).</b> Mild-to-profound developmental delay and intellectual disability</div></li><li class="half_rhythm"><div>
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<b>Neuromuscular features</b>
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</div><ul><li class="half_rhythm"><div>Hypotonia, axial or generalized</div></li><li class="half_rhythm"><div>Dystonia</div></li><li class="half_rhythm"><div>Muscle atrophy</div></li></ul></li><li class="half_rhythm"><div>
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<b>Sensorineural hearing impairment</b>
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</div></li><li class="half_rhythm"><div>
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<b>Feeding and growth issues</b>
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</div><ul><li class="half_rhythm"><div>Feeding difficulties</div></li><li class="half_rhythm"><div>Growth deficiency affecting both weight gain and linear growth</div></li></ul></li></ul><p>
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<b>Brain MRI findings</b>
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</p><ul><li class="half_rhythm"><div>Basal ganglia hyperintensities</div></li><li class="half_rhythm"><div>Cerebral atrophy</div></li><li class="half_rhythm"><div>Leukoencephalopathy</div></li></ul><p>
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<b>Supportive laboratory findings</b>
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</p><ul><li class="half_rhythm"><div><b>Urine organic acid analysis</b> [<a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al 2016</a>]</div><ul><li class="half_rhythm"><div>Elevation of methylmalonic acid (MMA) in most affected children. However, the MMA level is considerably less pronounced than in classic methylmalonic aciduria and can be only marginally elevated or even normal on rare occasions.</div></li><li class="half_rhythm"><div>Other metabolites that may be elevated in urine include methylcitrate, 3-methylglutaconic acid, 3-hydroxyisovaleric acid, and Krebs cycle intermediates such as succinate, fumarate, and 2-ketoglutarate.</div></li></ul></li><li class="half_rhythm"><div><b>Plasma MMA level</b> is more sensitive than organic acid analysis. Elevated plasma MMA has been reported even in those with marginally elevated urine MMA level [<a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</div></li><li class="half_rhythm"><div><b>Plasma acylcarnitine profile.</b> Elevated C3</div></li><li class="half_rhythm"><div><b>Plasma and cerebrospinal fluid lactate levels.</b> Elevated in most affected individuals</div></li></ul><p><b>Muscle biopsy findings.</b> In most cases muscle biopsy is not needed; however, muscle biopsy can be considered when molecular testing reveals variants of uncertain significance and further evidence is needed to confirm the diagnosis (see <a href="#sucla2-def.Molecular_Pathogenesis">Molecular Pathogenesis</a>, <b>Specific laboratory technical considerations</b>).</p><p><b>Family history</b> is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.</p></div><div id="sucla2-def.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>SUCLA2</i>-related mtDNA depletion syndrome <b>is established</b> in a proband with <a href="#sucla2-def.Suggestive_Findings">suggestive findings</a> and biallelic pathogenic (or likely pathogenic) variants in <i>SUCLA2</i> identified by molecular genetic testing (see <a href="/books/NBK6803/table/sucla2-def.T.molecular_genetic_testing_u/?report=objectonly" target="object" rid-ob="figobsucla2defTmoleculargenetictestingu">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bibr" href="#sucla2-def.REF.richards.2015.405" rid="sucla2-def.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include likely pathogenic variants. (2) Identification of biallelic <i>SUCLA2</i> variants of uncertain significance (or of one known <i>SUCLA2</i> pathogenic variant and one <i>SUCLA2 v</i>ariant of uncertain significance) does not establish or rule out the diagnosis.</p><p><b>Molecular genetic testing approaches</b> can include a combination of <b>gene-targeted testing</b> (single-gene testing, multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see <a href="#sucla2-def.Option_1">Option 1</a>), whereas comprehensive genomic testing does not (see <a href="#sucla2-def.Option_2">Option 2</a>).</p><div id="sucla2-def.Option_1"><h4>Option 1</h4><p>When the phenotypic and laboratory findings suggest the diagnosis of <i>SUCLA2</i>-related mtDNA depletion syndrome, molecular genetic testing approaches can include <b>single-gene testing</b> or use of a <b>multigene panel</b>.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-gene testing.</b> Sequence analysis of <i>SUCLA2</i> is performed first to detect missense, nonsense, and splice site variants and small intragenic deletions/insertions. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.</div><div class="half_rhythm">Note: Targeted analysis for the c.534+1G>A pathogenic founder variant can be performed first in probands of Faroese ancestry (see <a href="/books/NBK6803/table/sucla2-def.T.sucla2_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobsucla2defTsucla2pathogenicvariants">Table 7</a>).</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A mitochondrial disease</b>
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<b>multigene panel</b> that includes <i>SUCLA2</i> and other genes of interest (see <a href="#sucla2-def.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene 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 exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul></div><div id="sucla2-def.Option_2"><h4>Option 2</h4><p><b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible. To date, the majority of <i>SUCLA2</i> pathogenic variants reported (e.g., missense, nonsense) are within the coding region and are likely to be identified on exome sequencing.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsucla2defTmoleculargenetictestingu"><a href="/books/NBK6803/table/sucla2-def.T.molecular_genetic_testing_u/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobsucla2defTmoleculargenetictestingu"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sucla2-def.T.molecular_genetic_testing_u"><a href="/books/NBK6803/table/sucla2-def.T.molecular_genetic_testing_u/?report=objectonly" target="object" rid-ob="figobsucla2defTmoleculargenetictestingu">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>SUCLA2</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria </p></div></div></div></div></div><div id="sucla2-def.Clinical_Characteristics"><h2 id="_sucla2-def_Clinical_Characteristics_">Clinical Characteristics</h2><div id="sucla2-def.Clinical_Description"><h3>Clinical Description</h3><p><i>SUCLA2</i>-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (<i>SUCLA2</i>-related mtDNA depletion syndrome) is characterized by onset of the following features in infancy: developmental delay, hypotonia, dystonia, muscular atrophy, sensorineural hearing impairment, growth failure, and feeding difficulties. Other less frequent features include choreoathetosis, muscle weakness, recurrent vomiting, ptosis, and kyphoscoliosis. The median survival is age 20 years; approximately 30% of affected individuals succumb during childhood.</p><p>To date, 61individuals have been identified with biallelic pathogenic variants in <i>SUCLA2</i>, including 50 cases reviewed by <a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al [2016]</a>, <a class="bibr" href="#sucla2-def.REF.maas.2016.27" rid="sucla2-def.REF.maas.2016.27">Maas et al [2016]</a>, <a class="bibr" href="#sucla2-def.REF.fang.2017.746" rid="sucla2-def.REF.fang.2017.746">Fang et al [2017]</a>, <a class="bibr" href="#sucla2-def.REF.garone.2017.246" rid="sucla2-def.REF.garone.2017.246">Garone et al [2017]</a>, <a class="bibr" href="#sucla2-def.REF.huang.2017.213" rid="sucla2-def.REF.huang.2017.213">Huang et al [2017]</a>, <a class="bibr" href="#sucla2-def.REF.kang.2020.409" rid="sucla2-def.REF.kang.2020.409">Kang et al [2020]</a>, <a class="bibr" href="#sucla2-def.REF.alkhater.2021.252" rid="sucla2-def.REF.alkhater.2021.252">Alkhater et al [2021]</a>, <a class="bibr" href="#sucla2-def.REF.hiramatsu.2022.4129" rid="sucla2-def.REF.hiramatsu.2022.4129">Hiramatsu et al [2022]</a>. The following description of the phenotypic features associated with this condition is based on these reports.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsucla2defTsucla2relatedmitochondrial"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobsucla2defTsucla2relatedmitochondrial"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sucla2-def.T.sucla2related_mitochondrial"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial/?report=objectonly" target="object" rid-ob="figobsucla2defTsucla2relatedmitochondrial">Table 2. </a></h4><p class="float-caption no_bottom_margin"><i>SUCLA2</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Frequency of Select Features </p></div></div><p>Children with <i>SUCLA2</i>-related mtDNA depletion syndrome typically have an uncomplicated prenatal course and birth, and present during infancy with delayed development and hypotonia.</p><p><b>Developmental delay (DD) and intellectual disability (ID).</b> Global developmental delay and intellectual disabilities occur in most affected children and vary from mild to severe.</p><p><b>Neuromuscular.</b> Hypotonia, first manifesting in infancy, is a presenting sign in most cases. Hypotonia can be axial or generalized. Dystonia and muscle atrophy also occur commonly. Other, less frequent neurologic manifestations include choreoathetosis, muscle weakness, hypertonia, epilepsy (including infantile spasms and generalized convulsions), myoclonus, and axonal peripheral neuropathy [<a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al 2016</a>, <a class="bibr" href="#sucla2-def.REF.maas.2016.27" rid="sucla2-def.REF.maas.2016.27">Maas et al 2016</a>, <a class="bibr" href="#sucla2-def.REF.fang.2017.746" rid="sucla2-def.REF.fang.2017.746">Fang et al 2017</a>, <a class="bibr" href="#sucla2-def.REF.garone.2017.246" rid="sucla2-def.REF.garone.2017.246">Garone et al 2017</a>, <a class="bibr" href="#sucla2-def.REF.huang.2017.213" rid="sucla2-def.REF.huang.2017.213">Huang et al 2017</a>, <a class="bibr" href="#sucla2-def.REF.kang.2020.409" rid="sucla2-def.REF.kang.2020.409">Kang et al 2020</a>, <a class="bibr" href="#sucla2-def.REF.alkhater.2021.252" rid="sucla2-def.REF.alkhater.2021.252">Alkhater et al 2021</a>, <a class="bibr" href="#sucla2-def.REF.hiramatsu.2022.4129" rid="sucla2-def.REF.hiramatsu.2022.4129">Hiramatsu et al 2022</a>].</p><p>Brain MRI typically shows basal ganglia hyperintensities (70%), cerebral atrophy (70%), and leukoencephalopathy (15%) [<a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p><p><b>Hearing.</b> Most affected children develop sensorineural hearing impairment; some benefit from a cochlear implant. Hearing impairment can be congenital or appear during early childhood [<a class="bibr" href="#sucla2-def.REF.huang.2017.213" rid="sucla2-def.REF.huang.2017.213">Huang et al 2017</a>, <a class="bibr" href="#sucla2-def.REF.alkhater.2021.252" rid="sucla2-def.REF.alkhater.2021.252">Alkhater et al 2021</a>].</p><p><b>Vision/ophthalmologic.</b> Ptosis, ophthalmoplegia, and strabismus are present in some individuals [<a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p><p><b>Feeding/gastrointestinal.</b> Feeding difficulties, often necessitating gastrostomy tube placement, occur commonly. Recurrent vomiting and gastroesophageal reflux disease occur occasionally.</p><p><b>Growth deficiency / poor weight gain and linear growth deficiency.</b> Birth weight and length are typically within the normal range. Feeding and gastrointestinal difficulties can contribute to subsequent growth deficiency. Ongoing postnatal growth restriction with low weight and length/height is common [<a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p><p><b>Respiratory.</b> Recurrent respiratory infections occur occasionally. Respiratory distress due to muscle weakness, obstructive sleep apnea, and tracheomalacia has also been reported [<a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p><p><b>Skeletal.</b> Progressive kyphoscoliosis has been reported occasionally and may require treatment. Joint contractures can develop in the extremities secondary to decreased movement.</p><p>
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<b>Other</b>
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</p><ul><li class="half_rhythm"><div>Hyperhidrosis [<a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al 2016</a>]</div></li><li class="half_rhythm"><div>Neonatal hypoglycemia [<a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al 2016</a>]</div></li></ul><p><b>Prognosis.</b> Life span is shortened, with median survival of age 20 years. Approximately 30% of affected individuals die during childhood [<a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p></div><div id="sucla2-def.GenotypePhenotype_Correlation"><h3>Genotype-Phenotype Correlations</h3><p>Biallelic <i>SUCLA2</i> pathogenic missense variants can result in some residual enzyme activity and hence are associated with a milder phenotype and a longer median survival (age 21 years), whereas biallelic loss-of-function <i>SUCLA2</i> variants (deletion, frameshift, and nonsense) are associated with a more severe phenotype and a shorter median survival (age 15 years) [<a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p></div><div id="sucla2-def.Prevalence"><h3>Prevalence</h3><p><i>SUCLA2</i>-related mtDNA depletion syndrome is rare; the exact prevalence is unknown. To date, 61 individuals of different ethnic origins have been reported (see <a href="#sucla2-def.Clinical_Description">Clinical Description</a>).</p><p>A founder pathogenic variant in families of Faroese ancestry has been identified (see <a href="/books/NBK6803/table/sucla2-def.T.sucla2_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobsucla2defTsucla2pathogenicvariants">Table 7</a>); the disorder has a high incidence (1:1,700) and a carrier frequency of 1:33 in the Faroe Islands [<a class="bibr" href="#sucla2-def.REF.ostergaard.2007.853" rid="sucla2-def.REF.ostergaard.2007.853">Ostergaard et al 2007</a>].</p></div></div><div id="sucla2-def.Genetically_Related_Allelic_D"><h2 id="_sucla2-def_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 germline pathogenic variants in <i>SUCLA2</i>.</p><p>A contiguous gene deletion involving <i>SUCLA2</i> and <i>RB1</i> occurring in <i>trans</i> with a <i>SUCLA2</i> pathogenic variant was reported in an individual with both <i>SUCLA2</i>-related mtDNA depletion syndrome and <a href="/books/n/gene/retinoblastoma/?report=reader">retinoblastoma</a> [<a class="bibr" href="#sucla2-def.REF.matilainen.2015.325" rid="sucla2-def.REF.matilainen.2015.325">Matilainen et al 2015</a>].</p></div><div id="sucla2-def.Differential_Diagnosis"><h2 id="_sucla2-def_Differential_Diagnosis_">Differential Diagnosis</h2><p><i>SUCLA2</i>-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (<i>SUCLA2</i>-related mtDNA depletion syndrome) needs to be differentiated from other mtDNA depletion syndromes, a genetically and clinically heterogeneous group of primarily autosomal recessive disorders that are characterized by a severe reduction in mtDNA content leading to impaired energy production in affected tissues and organs (see <a href="/books/NBK6803/table/sucla2-def.T.mitochondrial_dna_depletion/?report=objectonly" target="object" rid-ob="figobsucla2defTmitochondrialdnadepletion">Table 3</a>).</p><p>Mitochondrial DNA depletion syndromes occur as a result of defects in mtDNA maintenance caused by pathogenic variants in nuclear genes that function in either mitochondrial nucleotide synthesis (<i>TK2</i>, <i>SUCLA2</i>, <i>SUCLG1</i>, <i>RRM2B</i>, <i>DGUOK</i>, and <i>TYMP</i>) or mtDNA replication (<i>POLG</i>, <i>TWNK</i>, <i>TFAM</i>, <i>RNASEH1</i>, <i>MGME1</i>) and are phenotypically classified into hepatocerebral, encephalomyopathic, encephaloneuropathic, neurogastrointestinal, and myopathic forms [<a class="bibr" href="#sucla2-def.REF.elhattab.2013.186" rid="sucla2-def.REF.elhattab.2013.186">El-Hattab & Scaglia 2013</a>]. See also the <a href="/books/n/gene/mtdna-md-ov/?report=reader">Mitochondrial DNA Maintenance Defects Overview.</a></p><p>The phenotype of <i>SUCLG1</i>-related mtDNA depletion syndrome may be difficult to distinguish from <i>SUCLA2</i>-related mtDNA depletion syndrome. <i>SUCLG1</i>-related mtDNA depletion syndrome is characterized by developmental delay, intellectual disability, hypotonia, muscle atrophy, feeding difficulties, growth restriction, dystonia, hearing loss, lactic acidosis, elevated urine and plasma methylmalonic acid, and mtDNA depletion. However, hepatopathy and cardiomyopathy occur in <i>SUCLG1</i>-related mtDNA depletion only.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsucla2defTmitochondrialdnadepletion"><a href="/books/NBK6803/table/sucla2-def.T.mitochondrial_dna_depletion/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobsucla2defTmitochondrialdnadepletion"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sucla2-def.T.mitochondrial_dna_depletion"><a href="/books/NBK6803/table/sucla2-def.T.mitochondrial_dna_depletion/?report=objectonly" target="object" rid-ob="figobsucla2defTmitochondrialdnadepletion">Table 3. </a></h4><p class="float-caption no_bottom_margin">Mitochondrial DNA Depletion Syndromes </p></div></div></div><div id="sucla2-def.Management"><h2 id="_sucla2-def_Management_">Management</h2><p>No clinical practice guidelines for <i>SUCLA2</i>-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (<i>SUCLA2</i>-related mtDNA depletion syndrome) have been published.</p><div id="sucla2-def.Evaluations_Following_Initial"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>SUCLA2</i>-related mtDNA depletion syndrome, the evaluations summarized in <a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_1/?report=objectonly" target="object" rid-ob="figobsucla2defTsucla2relatedmitochondrial1">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsucla2defTsucla2relatedmitochondrial1"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_1/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobsucla2defTsucla2relatedmitochondrial1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sucla2-def.T.sucla2related_mitochondrial_1"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_1/?report=objectonly" target="object" rid-ob="figobsucla2defTsucla2relatedmitochondrial1">Table 4. </a></h4><p class="float-caption no_bottom_margin"><i>SUCLA2</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Recommended Evaluations Following Initial Diagnosis </p></div></div></div><div id="sucla2-def.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>There is no cure for <i>SUCLA2</i>-related mitochondrial mtDNA depletion syndrome.</p><p><b>Supportive care</b> 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/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_2/?report=objectonly" target="object" rid-ob="figobsucla2defTsucla2relatedmitochondrial2">Table 5</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsucla2defTsucla2relatedmitochondrial2"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_2/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobsucla2defTsucla2relatedmitochondrial2"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sucla2-def.T.sucla2related_mitochondrial_2"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_2/?report=objectonly" target="object" rid-ob="figobsucla2defTsucla2relatedmitochondrial2">Table 5. </a></h4><p class="float-caption no_bottom_margin"><i>SUCLA2</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Treatment of Manifestations </p></div></div><div id="sucla2-def.Developmental_Delay__Intellec"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</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><div id="sucla2-def.Surveillance"><h3>Surveillance</h3><p>To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in <a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_3/?report=objectonly" target="object" rid-ob="figobsucla2defTsucla2relatedmitochondrial3">Table 6</a> are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsucla2defTsucla2relatedmitochondrial3"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_3/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobsucla2defTsucla2relatedmitochondrial3"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sucla2-def.T.sucla2related_mitochondrial_3"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_3/?report=objectonly" target="object" rid-ob="figobsucla2defTsucla2relatedmitochondrial3">Table 6. </a></h4><p class="float-caption no_bottom_margin"><i>SUCLA2</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Recommended Surveillance </p></div></div></div><div id="sucla2-def.Evaluation_of_Relatives_at_Ri"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#sucla2-def.Related_Genetic_Counseling_Is">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="sucla2-def.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 access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="sucla2-def.Genetic_Counseling"><h2 id="_sucla2-def_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="sucla2-def.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>SUCLA2</i>-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (<i>SUCLA2</i>-related mtDNA depletion syndrome) is inherited in an autosomal recessive manner.</p></div><div id="sucla2-def.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The parents of an affected child are presumed to be heterozygous for a <i>SUCLA2</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of the proband to confirm that both parents are heterozygous for a <i>SUCLA2</i> pathogenic variant and to allow reliable recurrence risk assessment. If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>One of the pathogenic variants identified in the proband occurred as a <i>de novo</i> event in the proband or as a postzygotic <i>de novo</i> event in a mosaic parent [<a class="bibr" href="#sucla2-def.REF.j_nsson.2017.519" rid="sucla2-def.REF.j_nsson.2017.519">Jónsson et al 2017</a>].</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental chromosome with the pathogenic variant resulted in homozygosity for the pathogenic variant in the proband.</div></li></ul></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for a <i>SUCLA2</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a proband.</b> To date, individuals with <i>SUCLA2</i>-related mtDNA depletion syndrome are not known to reproduce.</p><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of a <i>SUCLA2</i> pathogenic variant.</p></div><div id="sucla2-def.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>SUCLA2</i> pathogenic variants in the family.</p></div><div id="sucla2-def.Related_Genetic_Counseling_Is"><h3>Related Genetic Counseling Issues</h3><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (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><li class="half_rhythm"><div>Carrier testing for the reproductive partners of known carriers should be considered, particularly if both partners are of the same ethnic background. A founder pathogenic variant in families of Faroese origin has been identified; the disorder has a high incidence (1:1,700) and a carrier frequency of 1:33 in the Faroe Islands (see <a href="/books/NBK6803/table/sucla2-def.T.sucla2_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobsucla2defTsucla2pathogenicvariants">Table 7</a>).</div></li></ul></div><div id="sucla2-def.Prenatal_Testing_and_Preimpla"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>SUCLA2</i> pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing for <i>SUCLA2</i>-related mtDNA depletion syndrome are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. 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="sucla2-def.Resources"><h2 id="_sucla2-def_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>The Charlie Gard Foundation</b>
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</div><div>United Kingdom</div><div><b>Email:</b> hello@thecharliegardfoundation.org</div><div>
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<a href="https://www.thecharliegardfoundation.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.thecharliegardfoundation.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>United Mitochondrial Disease Foundation</b>
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</div><div><b>Phone:</b> 888-317-UMDF (8633)</div><div><b>Email:</b> info@umdf.org</div><div>
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<a href="https://www.umdf.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.umdf.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Human Disease Gene Website Series - Registry</b>
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</div><div>
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<a href="https://humandiseasegenes.nl/sucla2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SUCLA2</a>
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</div></li><li class="half_rhythm"><div>
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<b>RDCRN Patient Contact Registry: North American Mitochondrial Disease Consortium</b>
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</div><div>
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<a href="https://www.rarediseasesnetwork.org/cms/namdc" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Patient Contact Registry</a>
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</div></li></ul>
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</div><div id="sucla2-def.Molecular_Genetics"><h2 id="_sucla2-def_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 class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsucla2defmolgenTA"><a href="/books/NBK6803/table/sucla2-def.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobsucla2defmolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sucla2-def.molgen.TA"><a href="/books/NBK6803/table/sucla2-def.molgen.TA/?report=objectonly" target="object" rid-ob="figobsucla2defmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsucla2defmolgenTB"><a href="/books/NBK6803/table/sucla2-def.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobsucla2defmolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sucla2-def.molgen.TB"><a href="/books/NBK6803/table/sucla2-def.molgen.TB/?report=objectonly" target="object" rid-ob="figobsucla2defmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria (View All in OMIM) </p></div></div><div id="sucla2-def.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>SUCLA2</i> encodes a subunit of succinyl-CoA ligase (SUCL). SUCL has two important metabolic functions. First, it is a mitochondrial tricarboxylic acid (Krebs) cycle enzyme that catalyzes the reversible conversion of succinyl-CoA and either ADP or GDP to succinate and either ATP or GTP. SUCL is composed of an alpha subunit, encoded by <i>SUCLG1</i>, and a beta subunit, encoded by either <i>SUCLA2</i> or <i>SUCLG2</i>. The alpha subunit forms a heterodimer with either of its beta subunits, resulting in an ADP-forming SUCL and a GDP-forming SUCL, respectively. Second, SUCL forms a complex with the mitochondrial nucleoside diphosphate kinase, which is involved in the synthesis of mitochondrial nucleotides. These nucleotides are then used to synthesize mitochondrial DNA.</p><p>The pathogenic variants lead to dysfunctional SUCL protein. As SUCL forms a complex with the mitochondrial nucleoside diphosphate kinase, the lack of this complex formation in SUCL deficiency can disturb the kinase function, resulting in decreased mitochondrial nucleotide synthesis and therefore decreased mitochondrial DNA (mtDNA) synthesis leading to mtDNA depletion [<a class="bibr" href="#sucla2-def.REF.elhattab.2017.1539" rid="sucla2-def.REF.elhattab.2017.1539">El-Hattab et al 2017</a>].</p><p><b>Mechanism of disease causation.</b> Loss of protein function</p><p><b>Specific laboratory technical considerations.</b> For <i>SUCLA2</i> variants of uncertain significance, findings on muscle biopsy that help confirm the diagnosis of <i>SUCLA2</i>-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria include:</p><ul><li class="half_rhythm"><div>Electron microscopic findings of increased fiber size variability, atrophic fibers, intracellular lipid accumulation, COX-deficient fibers, and structurally altered mitochondria with abnormal cristae.</div></li><li class="half_rhythm"><div>Deficiencies in electron transport chain activity in combined complex I and IV; in combined complex I, III, and IV; and in isolated complex IV.</div></li><li class="half_rhythm"><div>Mitochondrial DNA content in affected muscle tissue typically reduced to 20%-60% of that in tissue- and age-matched controls.</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsucla2defTsucla2pathogenicvariants"><a href="/books/NBK6803/table/sucla2-def.T.sucla2_pathogenic_variants/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobsucla2defTsucla2pathogenicvariants"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sucla2-def.T.sucla2_pathogenic_variants"><a href="/books/NBK6803/table/sucla2-def.T.sucla2_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobsucla2defTsucla2pathogenicvariants">Table 7. </a></h4><p class="float-caption no_bottom_margin"><i>SUCLA2</i> Pathogenic Variants Referenced in This <i>GeneReview</i> </p></div></div></div></div><div id="sucla2-def.Chapter_Notes"><h2 id="_sucla2-def_Chapter_Notes_">Chapter Notes</h2><div id="sucla2-def.Author_Notes"><h3>Author Notes</h3><p><b>Dr Ayman El-Hattab</b> (<a href="mailto:dev@null" data-email="moc.oohay@wabattahle" class="oemail">moc.oohay@wabattahle</a>) is actively involved in clinical research regarding individuals with mitochondrial disorders. He would be happy to communicate with persons who have any questions regarding diagnosis of mitochondrial disorders or other considerations.</p><p>Dr El-Hattab is also interested in hearing from clinicians treating families affected by mitochondrial disorders in whom no causative variant has been identified through molecular genetic testing of the genes known to be involved in this group of disorders.</p><p>Contact Dr El-Hattab to inquire about review of <i>SUCLA2</i> variants of uncertain significance.</p></div><div id="sucla2-def.Author_History"><h3>Author History</h3><p>Ayman W El-Hattab, MD, FAAP, FACMG (2016-present)<br />Elsebet Ostergaard, MD, PhD; National University Hospital Rigshospitalet (2009-2016)<br />Fernando Scaglia, MD, FAAP, FACMG (2016-present)</p></div><div id="sucla2-def.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>28 September 2023 (bp) Comprehensive update posted live</div></li><li class="half_rhythm"><div>30 June 2016 (ma) Comprehensive update posted live</div></li><li class="half_rhythm"><div>26 May 2009 (et) Review posted live</div></li><li class="half_rhythm"><div>16 January 2009 (eo) Original submission</div></li></ul></div></div><div id="sucla2-def.References"><h2 id="_sucla2-def_References_">References</h2><div id="sucla2-def.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="sucla2-def.REF.alkhater.2021.252">Alkhater
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[<a href="/pmc/articles/PMC7497289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32596782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32596782</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK6803_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Ayman W El-Hattab</span>, MD, FAAP, FACMG<div class="affiliation small">Professor, Department of Clinical Sciences<br />College of Medicine<br />University of Sharjah<br />Sharjah, United Arab Emirates<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.oohay@wabattahle" class="oemail">moc.oohay@wabattahle</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Fernando Scaglia</span>, MD, FAAP, FACMG<div class="affiliation small">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@ailgacsf" class="oemail">ude.mcb@ailgacsf</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">May 26, 2009</span>; Last Update: <span itemprop="dateModified">September 28, 2023</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
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Washington) are included with each copy; (ii) a link to the original material is provided
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whenever the material is published elsewhere on the Web; and (iii) reproducers,
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distributors, and/or translators comply with the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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of GeneReviews chapters for use in lab reports and clinic notes are a permitted
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use.</p><p class="small">For more information, see the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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Disclaimer</a>.</p><p class="small">For questions regarding permissions or whether a specified use is allowed,
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>El-Hattab AW, Scaglia F. SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria. 2009 May 26 [Updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/stxbp1-ee/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/suclg1-mtddepl/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobsucla2defTmoleculargenetictestingu"><div id="sucla2-def.T.molecular_genetic_testing_u" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>SUCLA2</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK6803/table/sucla2-def.T.molecular_genetic_testing_u/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sucla2-def.T.molecular_genetic_testing_u_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sucla2-def.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_sucla2-def.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_sucla2-def.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_sucla2-def.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>SUCLA2</i>
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</td><td headers="hd_h_sucla2-def.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_sucla2-def.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">90% <sup>4</sup></td></tr><tr><td headers="hd_h_sucla2-def.T.molecular_genetic_testing_u_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_sucla2-def.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10% <sup>4</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="sucla2-def.TF.1.1"><p class="no_margin">See <a href="/books/NBK6803/?report=reader#sucla2-def.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="sucla2-def.TF.1.2"><p class="no_margin">See <a href="#sucla2-def.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="sucla2-def.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="sucla2-def.TF.1.4"><p class="no_margin">Data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#sucla2-def.REF.stenson.2020.1197" rid="sucla2-def.REF.stenson.2020.1197">Stenson et al 2020</a>], <a class="bibr" href="#sucla2-def.REF.carrozzo.2016.243" rid="sucla2-def.REF.carrozzo.2016.243">Carrozzo et al [2016]</a>, <a class="bibr" href="#sucla2-def.REF.maas.2016.27" rid="sucla2-def.REF.maas.2016.27">Maas et al [2016]</a>, <a class="bibr" href="#sucla2-def.REF.fang.2017.746" rid="sucla2-def.REF.fang.2017.746">Fang et al [2017]</a>, <a class="bibr" href="#sucla2-def.REF.garone.2017.246" rid="sucla2-def.REF.garone.2017.246">Garone et al [2017]</a>, <a class="bibr" href="#sucla2-def.REF.huang.2017.213" rid="sucla2-def.REF.huang.2017.213">Huang et al [2017]</a>, <a class="bibr" href="#sucla2-def.REF.kang.2020.409" rid="sucla2-def.REF.kang.2020.409">Kang et al [2020]</a>, <a class="bibr" href="#sucla2-def.REF.alkhater.2021.252" rid="sucla2-def.REF.alkhater.2021.252">Alkhater et al [2021]</a>, and <a class="bibr" href="#sucla2-def.REF.hiramatsu.2022.4129" rid="sucla2-def.REF.hiramatsu.2022.4129">Hiramatsu et al [2022]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="sucla2-def.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsucla2defTsucla2relatedmitochondrial"><div id="sucla2-def.T.sucla2related_mitochondrial" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>SUCLA2</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sucla2-def.T.sucla2related_mitochondrial_lrgtbl__"><table><thead><tr><th id="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature</th></tr></thead><tbody><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental delay / intellectual disability</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">95%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Regression</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="9" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neuromuscular</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypotonia</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">90%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Dystonia</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">80%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Muscle atrophy</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">40%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Choreoathetosis</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Muscle weakness</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypertonia</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Epilepsy</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Myoclonus</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Neuropathy</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Sensorineural hearing impairment</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">90%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Feeding/gastrointestinal</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feeding difficulties</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">50%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Recurrent vomiting</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gastroesophageal reflux disease</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Growth deficiency</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">90%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Vision/ophthalmologic</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ptosis</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Ophthalmoplegia</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Strabismus</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Respiratory</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Respiratory distress</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Recurrent respiratory infections</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skeletal</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Kyphoscoliosis</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Joint contractures</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Other</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypoglycemia</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hyperhidrosis</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobsucla2defTmitochondrialdnadepletion"><div id="sucla2-def.T.mitochondrial_dna_depletion" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Mitochondrial DNA Depletion Syndromes</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK6803/table/sucla2-def.T.mitochondrial_dna_depletion/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sucla2-def.T.mitochondrial_dna_depletion_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Phenotype <sup>1</sup></th><th id="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder/Phenotype</th><th id="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Additional Common Manifestations <sup>2</sup></th></tr></thead><tbody><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_1" rowspan="5" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hepatocerebral (Encephalohepatopathic)</b>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DGUOK</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DGUOK deficiency</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD, hypotonia, nystagmus, lactic acidosis</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>POLG</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/alpers/?report=reader">Alpers-Huttenlocher syndrome</a>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD, psychomotor regression, epilepsy, hearing impairment</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>MPV17</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/mpv17-mtdep/?report=reader">MPV17 deficiency</a>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD, hypotonia, poor weight gain, hearing impairment, lactic acidosis</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>TWNK</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Encephalohepatopathy (OMIM <a href="https://omim.org/entry/271245" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">271245</a>)</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD, hypotonia, lactic acidosis</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>TFAM</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Encephalohepatopathy (OMIM <a href="https://omim.org/entry/617156" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617156</a>)</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">IUGR, hypoglycemia</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_1" rowspan="6" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Encephalomyopathic</b>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>FBXL4</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/fbxl4-mtddepl/?report=reader">FBXL4 deficiency</a>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD, hypotonia, epilepsy, hearing impairment, lactic acidosis</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>SUCLG1</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/suclg1-mtddepl/?report=reader">SUCLG1 deficiency</a>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD, hypotonia, hearing impairment, ↑ MMA</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>RRM2B</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/rrm2b-mtddepl/?report=reader"><i>RRM2B</i> encephalomyopathic MDMD</a>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD, hypotonia, GI dysmotility, renal tubulopathy</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>OPA1</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Encephalomyopathy (OMIM <a href="https://omim.org/entry/616896" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616896</a>)</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD, HCM, optic atrophy</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>ABAT</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Encephalomyopathy w/↑ GABA (OMIM <a href="https://omim.org/entry/613163" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">613163</a>)</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD, hypotonia, epilepsy, ↑ GABA in plasma, urine, & CSF</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>RNASEH1</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Encephalomyopathy (OMIM <a href="https://omim.org/entry/616479" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616479</a>)</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmoplegia, ptosis, ataxia</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurogastrointestinal encephalopathic</b>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TYMP</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/mngie/?report=reader">MNGIE type 1</a>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">GI dysmotility, cachexia, peripheral neuropathy, ophthalmoplegia, muscle weakness, leukoencephalopathy <sup>3</sup></td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>POLG</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/alpers/?report=reader">MNGIE type 4B</a>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>RRM2B</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/rrm2b-mtddepl/?report=reader">MNGIE type 8B</a>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Myopathic</b>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TK2</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/tk2-mtddepl/?report=reader">TK2 deficiency</a>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypotonia, loss of acquired motor skills</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>AGK</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sengers syndrome (OMIM <a href="https://omim.org/entry/212350" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">212350</a>)</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypotonia, HCM, cataracts</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>MGME1</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Myopathy (OMIM <a href="https://omim.org/entry/615084" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">615084</a>)</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ptosis, ophthalmoplegia</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>SLC25A4</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiomyopathy (OMIM <a href="https://www.omim.org/entry/617184" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617184</a>)</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypotonia, HCM<br />(Mitochondrial DNA depletion phenotype is assoc w/autosomal dominant inheritance.)</td></tr><tr><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Encephaloneuropathic</b>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TWNK</i>
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</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infantile-onset spinocerebellar ataxia (OMIM <a href="https://www.omim.org/entry/271245" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">271245</a>)</td><td headers="hd_h_sucla2-def.T.mitochondrial_dna_depletion_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypotonia, hearing impairment</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">CSF = cerebrospinal fluid; DD = developmental delay; GABA = gamma-aminobutyric acid; GI = gastrointestinal; HCM = hypertrophic cardiomyopathy; IUGR = intrauterine growth restriction; MDMD = mitochondrial DNA maintenance defect; MMA = methylmalonic acid; MNGIE = mitochondrial neurogastrointestinal encephalopathy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="sucla2-def.TF.3.1"><p class="no_margin">Within each phenotypic category, mitochondrial DNA depletion syndromes are ordered by relative prevalence.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="sucla2-def.TF.3.2"><p class="no_margin">Common manifestations seen in addition to the primary phenotype (i.e., in addition to encephalohepatopathy, encephalomyopathy, etc.)</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="sucla2-def.TF.3.3"><p class="no_margin">Leukoencephalopathy is not present in <i>POLG</i>-related neurogastrointestinal encephalopathy.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsucla2defTsucla2relatedmitochondrial1"><div id="sucla2-def.T.sucla2related_mitochondrial_1" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p><i>SUCLA2</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sucla2-def.T.sucla2related_mitochondrial_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sucla2-def.T.sucla2related_mitochondrial_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_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_sucla2-def.T.sucla2related_mitochondrial_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_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_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>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neuromuscular</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic eval</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl assessment for hypotonia, dystonia, hypertonia, muscle weakness, muscle atrophy, movement disorders, & clinical signs of seizures</div></li><li class="half_rhythm"><div>Brain MRI</div></li><li class="half_rhythm"><div>Consider EMG to assess myopathy.</div></li><li class="half_rhythm"><div>Consider EEG if seizures are a concern.</div></li></ul>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT eval</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl assessment of:
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<ul><li class="half_rhythm"><div>Gross motor & fine motor skills</div></li><li class="half_rhythm"><div>Mobility, ADL, & need for adaptive devices</div></li><li class="half_rhythm"><div>Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)</div></li></ul>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hearing</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic eval</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for sensorineural hearing loss</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Feeding/</b>
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<br />
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<b>Gastrointestinal</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterology / nutrition / feeding team eval</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl eval of swallowing function / aspiration risk, nutritional status, & GERD</div></li><li class="half_rhythm"><div>Consider eval for gastrostomy tube placement in affected persons w/dysphagia &/or aspiration risk.</div></li></ul>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Growth</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Measure weight, length/height, & head circumference; review growth charts.</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for growth deficiency / failure to thrive</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Vision/Ophthalmologic</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for reduced vision, ophthalmoplegia, ptosis, & strabismus that may require referral for subspecialty care &/or low vision services</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Respiratory</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pulmonary eval</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for sleep apnea</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skeletal</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT eval</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl assessment of:
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<ul><li class="half_rhythm"><div>Gross motor & fine motor skills</div></li><li class="half_rhythm"><div>Joint contractures & kyphoscoliosis</div></li><li class="half_rhythm"><div>Mobility, ADL, & need for adaptive devices</div></li><li class="half_rhythm"><div>Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)</div></li></ul>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic counseling</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_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_sucla2-def.T.sucla2related_mitochondrial_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 <i>SUCLA2</i>-related mtDNA depletion syndrome to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family support</b>
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<br />
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<b>& resources</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
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<ul><li class="half_rhythm"><div>Community or <a href="#sucla2-def.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></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ADHD = attention-deficit/hyperactivity disorder; ADL = activities of daily living; ASD = autism spectrum disorder; GERD = gastroesophageal reflux disease; MOI = mode of inheritance; mtDNA = mitochondrial DNA; OT = occupational therapy; PT = physical therapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="sucla2-def.TF.4.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsucla2defTsucla2relatedmitochondrial2"><div id="sucla2-def.T.sucla2related_mitochondrial_2" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p><i>SUCLA2</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sucla2-def.T.sucla2related_mitochondrial_2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_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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<br />
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<b>Intellectual disability</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#sucla2-def.Developmental_Delay__Intellec">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dystonia</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standardized treatment for dystonia by experienced neurologist</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hypertonia/Spasticity</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT incl stretching to help avoid contractures & falls</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider need for positioning & mobility devices, disability parking placard.</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Epilepsy</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standardized treatment w/ASM by experienced neurologist</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Many ASMs may be effective; none has been demonstrated effective specifically for this disorder.</div></li><li class="half_rhythm"><div>Education of parents/caregivers <sup>1</sup></div></li></ul>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Sensorineural hearing impairment</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing aids &/or cochlear implantation may be helpful per otolaryngologist & audiologist.</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Community hearing services through early intervention or school district</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Feeding difficulties / GERD / Growth deficiency / Failure to thrive</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Nutritional support by dietitian</div></li><li class="half_rhythm"><div>Feeding therapy</div></li><li class="half_rhythm"><div>Gastrostomy tube placement may be required for persistent feeding issues.</div></li></ul>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Low threshold for clinical feeding eval &/or radiographic swallowing study when showing clinical signs or symptoms of dysphagia</div></li><li class="half_rhythm"><div>Intervention for GERD/vomiting as indicated</div></li></ul>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Vision/Ophthalmologic</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologist</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Strabismus, ptosis, ophthalmoplegia</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Ophthalmic subspecialist</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Blepharoplasty for significant ptosis</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Low vision services</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Children: through early intervention programs &/or school district</div></li><li class="half_rhythm"><div>Adults: low vision clinic &/or community vision services / OT / mobility services</div></li></ul>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Respiratory</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Chest physiotherapy</div></li><li class="half_rhythm"><div>Aggressive antibiotic treatment of chest infections</div></li></ul>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Artificial ventilation (incl assisted nasal ventilation or intubation & use of tracheostomy & ventilator) for respiratory insufficiency (See <b>Ethics consultation</b> in this table.)</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skeletal</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>PT to help maintain muscle function & prevent joint contractures</div></li><li class="half_rhythm"><div>Bracing or surgery for kyphoscoliosis per orthopedist</div></li></ul>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family/Community</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ensure appropriate social work involvement to connect families w/local resources, respite, & support.</div></li><li class="half_rhythm"><div>Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.</div></li></ul>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ongoing assessment of need for palliative care involvement &/or home nursing</div></li><li class="half_rhythm"><div>Consider involvement in adaptive sports or <a href="https://www.specialolympics.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Special Olympics</a>.</div></li></ul>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ethics consultation</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical ethics services</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Assess health care decisions in the context of the best interest of the child & values & preferences of the family.</div></li><li class="half_rhythm"><div>For difficult life-prolonging decisions or for clarification of treatment options, consider further consultation w/independent clinical teams. <sup>2</sup></div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ASM = antiseizure medication; GERD = gastroesophageal reflux disease; OT = occupational therapy; PT = physical therapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="sucla2-def.TF.5.1"><p class="no_margin">Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see <a href="https://www.epilepsy.com/tools-resources/forms-resources#Epilepsy-Foundation-Toolbox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy Foundation Toolbox</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="sucla2-def.TF.5.2"><p class="no_margin">
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<a class="bibr" href="#sucla2-def.REF.linney.2019.413" rid="sucla2-def.REF.linney.2019.413">Linney et al [2019]</a>
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</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsucla2defTsucla2relatedmitochondrial3"><div id="sucla2-def.T.sucla2related_mitochondrial_3" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p><i>SUCLA2</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK6803/table/sucla2-def.T.sucla2related_mitochondrial_3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sucla2-def.T.sucla2related_mitochondrial_3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_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_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_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_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neuromuscular</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor those w/dystonia, hypertonia, muscle atrophy, muscle weakness, choreoathetosis, or seizures as clinically indicated.</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating neurologist</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Assess for new manifestations such as changes in muscle tone, emergence of movement disorders, or signs of seizures.</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_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_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hearing</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor hearing status.</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating otolaryngologist & audiologist</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Feeding/Gastrointestinal</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Eval of safety of oral intake</div></li><li class="half_rhythm"><div>Monitor for GERD/vomiting.</div></li></ul>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_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_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Growth</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Measurement of growth parameters</div></li><li class="half_rhythm"><div>Eval of nutritional status</div></li></ul>
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</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Vision/Ophthalmologic</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor vision, ocular alignment/movement, & ptosis.</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating ophthalmologist(s)</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Low vision services</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating clinicians</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Respiratory</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for evidence of aspiration, respiratory insufficiency.</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_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_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skeletal</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor those w/scoliosis or joint contractures for progression.</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating orthopedist</td></tr><tr><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Monitor for new development of kyphoscoliosis or joint contractures.</div></li><li class="half_rhythm"><div>Physical medicine, OT/PT assessment of mobility, self-help skills</div></li></ul>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_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_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family/Community</b>
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</td><td headers="hd_h_sucla2-def.T.sucla2related_mitochondrial_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning).</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">GERD = gastroesophageal reflux disease; OT = occupational therapy; PT = physical therapy</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsucla2defmolgenTA"><div id="sucla2-def.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK6803/table/sucla2-def.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sucla2-def.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_sucla2-def.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_sucla2-def.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_sucla2-def.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_sucla2-def.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_sucla2-def.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_sucla2-def.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_sucla2-def.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/8803" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>SUCLA2</i>
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</a>
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</td><td headers="hd_b_sucla2-def.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=8803" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">13q14<wbr style="display:inline-block"></wbr>​.2</a>
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</td><td headers="hd_b_sucla2-def.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.uniprot.org/uniprot/Q9P2R7" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Succinate--CoA ligase [ADP-forming] subunit beta, mitochondrial</a>
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</td><td headers="hd_b_sucla2-def.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://databases.lovd.nl/shared/genes/SUCLA2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SUCLA2 database</a>
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</td><td headers="hd_b_sucla2-def.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=SUCLA2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SUCLA2</a>
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</td><td headers="hd_b_sucla2-def.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=SUCLA2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SUCLA2</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="sucla2-def.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
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chromosome locus from
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsucla2defmolgenTB"><div id="sucla2-def.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria (<a href="/omim/603921,612073" 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/NBK6803/table/sucla2-def.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sucla2-def.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/603921" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">603921</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SUCCINATE-CoA LIGASE, ADP-FORMING, SUBUNIT BETA; SUCLA2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/612073" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">612073</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MITOCHONDRIAL DNA DEPLETION SYNDROME 5 (ENCEPHALOMYOPATHIC WITH OR WITHOUT METHYLMALONIC ACIDURIA); MTDPS5</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobsucla2defTsucla2pathogenicvariants"><div id="sucla2-def.T.sucla2_pathogenic_variants" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p><i>SUCLA2</i> Pathogenic Variants Referenced in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK6803/table/sucla2-def.T.sucla2_pathogenic_variants/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sucla2-def.T.sucla2_pathogenic_variants_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sucla2-def.T.sucla2_pathogenic_variants_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_sucla2-def.T.sucla2_pathogenic_variants_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_sucla2-def.T.sucla2_pathogenic_variants_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_sucla2-def.T.sucla2_pathogenic_variants_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_sucla2-def.T.sucla2_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_003850.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_003850<wbr style="display:inline-block"></wbr>​.2</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_003841.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_003841<wbr style="display:inline-block"></wbr>​.1</a>
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</td><td headers="hd_h_sucla2-def.T.sucla2_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.534+1G>A</td><td headers="hd_h_sucla2-def.T.sucla2_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_sucla2-def.T.sucla2_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Faroe Islands [<a class="bibr" href="#sucla2-def.REF.carrozzo.2007.862" rid="sucla2-def.REF.carrozzo.2007.862">Carrozzo et al 2007</a>, <a class="bibr" href="#sucla2-def.REF.ostergaard.2007.853" rid="sucla2-def.REF.ostergaard.2007.853">Ostergaard et al 2007</a>, <a class="bibr" href="#sucla2-def.REF.morava.2009.438" rid="sucla2-def.REF.morava.2009.438">Morava et al 2009</a>]</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><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></dl><dl class="bkr_refwrap"><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/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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