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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="SUCLG1-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="2017/03/30">
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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="SUCLG1 Deficiency">
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<meta name="citation_keywords" content="SUCLG1-Related Succinyl-CoA Ligase Deficiency">
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<meta name="citation_keywords" content="SUCLG1 Deficiency">
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<meta name="citation_keywords" content="SUCLG1-Related Succinyl-CoA Ligase Deficiency">
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<meta name="citation_keywords" content="Succinate--CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial">
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<meta name="citation_keywords" content="SUCLG1">
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<meta name="citation_keywords" content="SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria">
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<meta name="DC.Title" content="SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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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="DC.Date" content="2017/03/30">
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<meta name="description" content="SUCLG1-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria is characterized in the majority of affected newborns by hypotonia, muscle atrophy, feeding difficulties, and lactic acidosis. Affected infants commonly manifest developmental delay / cognitive impairment, growth retardation / failure to thrive, hepatopathy, sensorineural hearing impairment, dystonia, and hypertonia. Notable findings in some affected individuals include hypertrophic cardiomyopathy, epilepsy, myoclonus, microcephaly, sleep disturbance, rhabdomyolysis, contractures, hypothermia, and/or hypoglycemia. Life span is shortened, with median survival of 20 months.">
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<meta name="og:description" content="SUCLG1-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria is characterized in the majority of affected newborns by hypotonia, muscle atrophy, feeding difficulties, and lactic acidosis. Affected infants commonly manifest developmental delay / cognitive impairment, growth retardation / failure to thrive, hepatopathy, sensorineural hearing impairment, dystonia, and hypertonia. Notable findings in some affected individuals include hypertrophic cardiomyopathy, epilepsy, myoclonus, microcephaly, sleep disturbance, rhabdomyolysis, contractures, hypothermia, and/or hypoglycemia. Life span is shortened, with median survival of 20 months.">
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id="jr-fip-info-p"><a id="jr-fip-prev" 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="_NBK425223_"><span class="title" itemprop="name"><i>SUCLG1</i>-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: SUCLG1 Deficiency, <i>SUCLG1</i>-Related Succinyl-CoA Ligase Deficiency</div><p class="contribs">El-Hattab AW, Scaglia F.</p><p class="fm-aai"><a href="#_NBK425223_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 16 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="suclg1-mtddepl.Summary" itemprop="description"><h2 id="_suclg1-mtddepl_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>SUCLG1</i>-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria is characterized in the majority of affected newborns by hypotonia, muscle atrophy, feeding difficulties, and lactic acidosis. Affected infants commonly manifest developmental delay / cognitive impairment, growth retardation / failure to thrive, hepatopathy, sensorineural hearing impairment, dystonia, and hypertonia. Notable findings in some affected individuals include hypertrophic cardiomyopathy, epilepsy, myoclonus, microcephaly, sleep disturbance, rhabdomyolysis, contractures, hypothermia, and/or hypoglycemia. Life span is shortened, with median survival of 20 months.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>SUCLG1</i>-related mtDNA depletion syndrome is established in a proband by the identification of biallelic pathogenic variants in <i>SUCLG1</i> on molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Management is supportive and is best provided by a multidisciplinary team. Treatment may include physical therapy to help maintain muscle function and prevent joint contractures, nutritional support by a dietitian, use of a nasogastric tube or gastrostomy tube feedings, chest physiotherapy, and aggressive antibiotic treatment of chest infections. When present, seizures are treated using standard anti-seizure medication.</p><p><i>Surveillance:</i> The suggested evaluations (with frequency varying according to the needs of the child) can include developmental and neurologic assessment, nutritional and growth assessment, echocardiogram, liver function tests, hearing evaluation, and ophthalmologic examination.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>SUCLG1</i>-related mtDNA depletion syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has 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>SUCLG1</i> pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.</p></div></div><div id="suclg1-mtddepl.Diagnosis"><h2 id="_suclg1-mtddepl_Diagnosis_">Diagnosis</h2><div id="suclg1-mtddepl.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>SUCLG1</i>-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria (MMA) typically manifests at birth or during early infancy and <b>should be suspected</b> in individuals with a combination of the following supportive clinical, brain MRI, laboratory, and muscle biopsy findings.</p><p>
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<b>Clinical features</b>
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</p><p>Present in >50%:</p><ul><li class="half_rhythm"><div>Developmental delay and cognitive impairment</div></li><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Muscle atrophy</div></li><li class="half_rhythm"><div>Feeding difficulties</div></li></ul><p>Present in 20%-50%:</p><ul><li class="half_rhythm"><div>Growth retardation / failure to thrive</div></li><li class="half_rhythm"><div>Hepatopathy</div></li><li class="half_rhythm"><div>Sensorineural hearing impairment</div></li><li class="half_rhythm"><div>Dystonia</div></li><li class="half_rhythm"><div>Hypertonia</div></li></ul><p>Present in <20%:</p><ul><li class="half_rhythm"><div>Hypertrophic cardiomyopathy</div></li><li class="half_rhythm"><div>Recurrent respiratory infections, respiratory distress, and apnea</div></li><li class="half_rhythm"><div>Recurrent vomiting and gastroesophageal reflux disease</div></li><li class="half_rhythm"><div>Ptosis and strabismus</div></li><li class="half_rhythm"><div>Epilepsy, myoclonus, and microcephaly</div></li><li class="half_rhythm"><div>Hyperhidrosis</div></li><li class="half_rhythm"><div>Sleep disturbance</div></li><li class="half_rhythm"><div>Rhabdomyolysis</div></li><li class="half_rhythm"><div>Contractures</div></li><li class="half_rhythm"><div>Hypothermia</div></li></ul><p><b>Brain MRI findings</b> [<a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>]</p><ul><li class="half_rhythm"><div>Basal ganglia hyperintensities (80%)</div></li><li class="half_rhythm"><div>Cerebral atrophy (30%)</div></li><li class="half_rhythm"><div>Leukoencephalopathy (20%)</div></li></ul><p>
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<b>Supportive laboratory findings</b>
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</p><ul><li class="half_rhythm"><div>
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<b>Urine organic acid analysis</b>
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</div><ul><li class="half_rhythm"><div class="half_rhythm">Elevation of urinary methylmalonic acid (MMA) in all affected children. Urinary MMA ranges from 10 to 500 mmol/mol creatinine (normal <3 mmol/mol creatinine).</div><div class="half_rhythm">Note: In classic <a href="/books/n/gene/mma/?report=reader">methylmalonic aciduria</a> urinary MMA is ~1,000-10,000 mmol/mol creatinine, and in defects of cobalamin metabolism urinary MMA is ~100s mmol/mol creatinine (see <a href="#suclg1-mtddepl.Differential_Diagnosis">Differential Diagnosis</a>).</div></li><li class="half_rhythm"><div class="half_rhythm">Several other metabolites that may be elevated in urine include methylcitrate, 3-methylglutaconic acid, 3-hydroxyisovaleric acid, and Krebs cycle intermediates (e.g., succinate, fumarate, 2-ketoglutarate).</div></li></ul></li><li class="half_rhythm"><div><b>Plasma MMA level</b> is elevated in all affected children and ranges from 1 to10 mmol/L (normal <0.3 mmol/L). Note: In classic <a href="/books/n/gene/mma/?report=reader">methylmalonic aciduria</a> plasma MMA is ~100-1,000 mmol/L, and in defects of cobalamin metabolism plasma MMA is ~10s mmol/L (see <a href="#suclg1-mtddepl.Differential_Diagnosis">Differential Diagnosis</a>).</div></li><li class="half_rhythm"><div><b>Acylcarnitine profile</b> can show elevated C3; thus, this condition can potentially be detected by newborn screening.</div></li><li class="half_rhythm"><div><b>Plasma and CSF lactate levels</b> are elevated in most affected individuals.</div></li><li class="half_rhythm"><div><b>Hypoglycemia</b> can occasionally occur [<a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</div></li></ul><p><b>Muscle biopsy</b>, typically performed during the evaluation of individuals with mitochondrial diseases, can show variable abnormalities or can occasionally be normal. The following findings can suggest the diagnosis:</p><ul><li class="half_rhythm"><div>Increased fiber size variability, atrophic fibers, intracellular lipid accumulation, ragged-red fibers (RRF), and COX-deficient fibers</div></li><li class="half_rhythm"><div>Structurally altered mitochondria with abnormal cristae on electron microscopy</div></li><li class="half_rhythm"><div>Abnormal electron transport chain activity. The most common abnormalities are combined complex I and IV deficiencies, combined complex I, III, and IV deficiencies, and isolated complex IV deficiency.</div></li><li class="half_rhythm"><div>Reduced mtDNA content; typically 15%-50% of tissue- and age-matched controls [<a class="bibr" href="#suclg1-mtddepl.REF.ostergaard.2007.383" rid="suclg1-mtddepl.REF.ostergaard.2007.383">Ostergaard et al 2007</a>, <a class="bibr" href="#suclg1-mtddepl.REF.valayannopoulos.2010.335" rid="suclg1-mtddepl.REF.valayannopoulos.2010.335">Valayannopoulos et al 2010</a>, <a class="bibr" href="#suclg1-mtddepl.REF.randolph.2011.149" rid="suclg1-mtddepl.REF.randolph.2011.149">Randolph et al 2011</a>, <a class="bibr" href="#suclg1-mtddepl.REF.landsverk.2014" rid="suclg1-mtddepl.REF.landsverk.2014">Landsverk et al 2014</a>]</div></li></ul></div><div id="suclg1-mtddepl.Establishing_the_Diagnosi"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>SUCLG1</i>-related mtDNA depletion syndrome <b>is established</b> in a proband by the identification of biallelic pathogenic (or likely pathogenic) variants in <i>SUCLG1</i> on molecular genetic testing (see <a href="/books/NBK425223/table/suclg1-mtddepl.T.molecular_genetic_testi/?report=objectonly" target="object" rid-ob="figobsuclg1mtddeplTmoleculargenetictesti">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="#suclg1-mtddepl.REF.richards.2015.405" rid="suclg1-mtddepl.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include likely pathogenic variants. (2) Identification of biallelic <i>SUCLG1</i> variants of uncertain significance (or of one known <i>SUCLG1</i> pathogenic variant and one <i>SUCLG1</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (multigene panel) and <b>genomic testing</b> (comprehensive genome sequencing) depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of <i>SUCLG1</i>-related mtDNA depletion syndrome is broad, children with the distinctive findings described in <a href="#suclg1-mtddepl.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#suclg1-mtddepl.Option_1">Option 1</a>), whereas those with a phenotype indistinguishable from other inherited mitochondrial disorders are more likely to be diagnosed using genomic testing (see <a href="#suclg1-mtddepl.Option_2">Option 2</a>).</p><div id="suclg1-mtddepl.Option_1"><h4>Option 1</h4><p>The phenotypes of <i>SUCLG1</i>-related mtDNA depletion syndrome and <i>SUCLA2</i>-related mtDNA depletion syndrome are difficult to distinguish and both are associated with elevated MMA. Therefore, when the phenotypic and laboratory findings suggest the diagnosis of <i>SUCLG1</i>-related mtDNA depletion syndrome, molecular genetic testing approaches can include <b><i>SUCLG1</i> and <i>SUCLA2</i> testing</b> or use of a <b>multigene panel</b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b><i>SUCLG1</i> and <i>SUCLA2</i> testing.</b> Sequence analysis of <i>SUCLG1</i> and <i>SUCLA2</i> is performed first. If only one pathogenic variant is found, gene-targeted deletion/duplication analysis of that gene could be considered; however, to date no exon or whole-gene deletions of either gene have been reported.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> that includes <i>SUCLG1</i>, <i>SUCLA2</i>, and other genes related to <b>mtDNA depletion syndromes</b> (see <a href="#suclg1-mtddepl.Differential_Diagnosis">Differential Diagnosis</a>) may also be considered. 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>; thus, clinicians need to determine which multigene panel 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. Of note, given the rarity of <i>SUCLG1</i>-related mtDNA depletion syndrome, some panels for mtDNA depletion syndromes may not include this gene. (3) 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="suclg1-mtddepl.Option_2"><h4>Option 2</h4><p>When the phenotype is indistinguishable from many other <b>inherited mitochondrial disorders</b>, molecular genetic testing approaches can include <b>genomic testing</b> (comprehensive genome sequencing) and/or <b>gene-targeted testing</b> (multigene panel):</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive genome sequencing</b> (when clinically available) includes exome sequencing and genome sequencing.</div><div class="half_rhythm">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>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> for <b>inherited mitochondrial disorders</b> may also be considered.</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsuclg1mtddeplTmoleculargenetictesti"><a href="/books/NBK425223/table/suclg1-mtddepl.T.molecular_genetic_testi/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobsuclg1mtddeplTmoleculargenetictesti"><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="suclg1-mtddepl.T.molecular_genetic_testi"><a href="/books/NBK425223/table/suclg1-mtddepl.T.molecular_genetic_testi/?report=objectonly" target="object" rid-ob="figobsuclg1mtddeplTmoleculargenetictesti">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>SUCLG1</i>-Related mtDNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria </p></div></div></div></div></div><div id="suclg1-mtddepl.Clinical_Characteristics"><h2 id="_suclg1-mtddepl_Clinical_Characteristics_">Clinical Characteristics</h2><div id="suclg1-mtddepl.Clinical_Description"><h3>Clinical Description</h3><p>To date 29 individuals with <i>SUCLG1</i>-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria (MMA) have been reported [<a class="bibr" href="#suclg1-mtddepl.REF.ostergaard.2007.383" rid="suclg1-mtddepl.REF.ostergaard.2007.383">Ostergaard et al 2007</a>, <a class="bibr" href="#suclg1-mtddepl.REF.ostergaard.2010.201" rid="suclg1-mtddepl.REF.ostergaard.2010.201">Ostergaard et al 2010</a>, <a class="bibr" href="#suclg1-mtddepl.REF.rivera.2010.362" rid="suclg1-mtddepl.REF.rivera.2010.362">Rivera et al 2010</a>, <a class="bibr" href="#suclg1-mtddepl.REF.rouzier.2010.670" rid="suclg1-mtddepl.REF.rouzier.2010.670">Rouzier et al 2010</a>, <a class="bibr" href="#suclg1-mtddepl.REF.valayannopoulos.2010.335" rid="suclg1-mtddepl.REF.valayannopoulos.2010.335">Valayannopoulos et al 2010</a>, <a class="bibr" href="#suclg1-mtddepl.REF.van_hove.2010.159" rid="suclg1-mtddepl.REF.van_hove.2010.159">Van Hove et al 2010</a>, <a class="bibr" href="#suclg1-mtddepl.REF.randolph.2011.149" rid="suclg1-mtddepl.REF.randolph.2011.149">Randolph et al 2011</a>, <a class="bibr" href="#suclg1-mtddepl.REF.sakamoto.2011.921" rid="suclg1-mtddepl.REF.sakamoto.2011.921">Sakamoto et al 2011</a>, <a class="bibr" href="#suclg1-mtddepl.REF.honzik.2012.749" rid="suclg1-mtddepl.REF.honzik.2012.749">Honzik et al 2012</a>, <a class="bibr" href="#suclg1-mtddepl.REF.navarrosastre.2012.409" rid="suclg1-mtddepl.REF.navarrosastre.2012.409">Navarro-Sastre et al 2012</a>, <a class="bibr" href="#suclg1-mtddepl.REF.landsverk.2014" rid="suclg1-mtddepl.REF.landsverk.2014">Landsverk et al 2014</a>, <a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>, <a class="bibr" href="#suclg1-mtddepl.REF.chu.2016.264" rid="suclg1-mtddepl.REF.chu.2016.264">Chu et al 2016</a>, <a class="bibr" href="#suclg1-mtddepl.REF.donti.2016.68" rid="suclg1-mtddepl.REF.donti.2016.68">Donti et al 2016</a>, <a class="bibr" href="#suclg1-mtddepl.REF.liu.2016.61" rid="suclg1-mtddepl.REF.liu.2016.61">Liu et al 2016</a>, <a class="bibr" href="#suclg1-mtddepl.REF.pupavac.2016.363" rid="suclg1-mtddepl.REF.pupavac.2016.363">Pupavac et al 2016</a>].</p><p>The clinical description here is based on the findings reported in these 29 individuals. The common clinical manifestations are summarized in <a href="/books/NBK425223/table/suclg1-mtddepl.T.clinical_manifestations/?report=objectonly" target="object" rid-ob="figobsuclg1mtddeplTclinicalmanifestations">Table 2</a> [<a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsuclg1mtddeplTclinicalmanifestations"><a href="/books/NBK425223/table/suclg1-mtddepl.T.clinical_manifestations/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobsuclg1mtddeplTclinicalmanifestations"><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="suclg1-mtddepl.T.clinical_manifestations"><a href="/books/NBK425223/table/suclg1-mtddepl.T.clinical_manifestations/?report=objectonly" target="object" rid-ob="figobsuclg1mtddeplTclinicalmanifestations">Table 2. </a></h4><p class="float-caption no_bottom_margin">Clinical Manifestations of <i>SUCLG1</i>-Related mtDNA Depletion Syndrome </p></div></div><p><b>Age of onset and phenotypic spectrum.</b> Although <i>SUCLG1</i>-related mtDNA depletion syndrome can present from the prenatal period to age one year, the majority of affected infants present at birth [<a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p><p>The majority have an uncomplicated pregnancy and normal birth weight; however, five neonates had intrauterine growth restriction (IUGR) or were small for gestational age (SGA) [<a class="bibr" href="#suclg1-mtddepl.REF.ostergaard.2007.383" rid="suclg1-mtddepl.REF.ostergaard.2007.383">Ostergaard et al 2007</a>, <a class="bibr" href="#suclg1-mtddepl.REF.randolph.2011.149" rid="suclg1-mtddepl.REF.randolph.2011.149">Randolph et al 2011</a>, <a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>]. Rare prenatal manifestations may include oligohydramnios and abnormal fetal heart rate [<a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p><p>The majority of affected infants present with early-onset encephalomyopathy and neurocognitive problems as well as hepatopathy, feeding and growth problems, and cardiorespiratory complications.</p><p>Death from severe metabolic acidosis during the neonatal period (fatal infantile lactic acidosis) has been reported in five infants [<a class="bibr" href="#suclg1-mtddepl.REF.ostergaard.2007.383" rid="suclg1-mtddepl.REF.ostergaard.2007.383">Ostergaard et al 2007</a>, <a class="bibr" href="#suclg1-mtddepl.REF.rivera.2010.362" rid="suclg1-mtddepl.REF.rivera.2010.362">Rivera et al 2010</a>].</p><p><b>Neurocognitive.</b> The majority of affected children demonstrate developmental delay, cognitive impairment, hypotonia, and muscle atrophy. Other, less frequent, neurologic manifestations include: sensorineural hearing impairment, dystonia, hypertonia, epilepsy, myoclonus, microcephaly, choreoathetosis, ptosis, and strabismus.</p><p><b>Hepatopathy.</b> Approximately 40% of affected individuals have liver involvement manifesting as hepatomegaly, steatosis, and elevated liver enzymes. One affected infant developed intermittent episodes of liver failure [<a class="bibr" href="#suclg1-mtddepl.REF.van_hove.2010.159" rid="suclg1-mtddepl.REF.van_hove.2010.159">Van Hove et al 2010</a>].</p><p><b>Feeding and growth.</b> Failure to thrive, growth retardation, and feeding difficulties, often necessitating tube feeding, occur commonly. Recurrent vomiting and gastroesophageal reflux disease (GERD) occasionally occur. The feeding difficulties, recurrent vomiting, and GERD can cause or contribute to growth failure.</p><p><b>Cardiac.</b> Hypertrophic cardiomyopathy was reported in 15% of affected children. Ventricular hypertrophy is typically mild and appears in the neonatal period or infancy [<a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p><p><b>Respiratory.</b> Recurrent respiratory infections are reported in some. Respiratory distress due to muscle weakness, apnea, and abnormal breathing has been reported.</p><p><b>Congenital malformations.</b> One affected infant had multiple congenital anomalies including cleft lip and palate, aortic coarctation, patent ductus arteriosus, patent foramen ovale, shortening of the left femur and both humeri, dilatation of the left renal collecting system, and accessory left kidney [<a class="bibr" href="#suclg1-mtddepl.REF.landsverk.2014" rid="suclg1-mtddepl.REF.landsverk.2014">Landsverk et al 2014</a>].</p><p>Other congenital anomalies reported in single infants each are interrupted aortic arch, polydactyly, and hypospadias [<a class="bibr" href="#suclg1-mtddepl.REF.ostergaard.2007.383" rid="suclg1-mtddepl.REF.ostergaard.2007.383">Ostergaard et al 2007</a>, <a class="bibr" href="#suclg1-mtddepl.REF.rivera.2010.362" rid="suclg1-mtddepl.REF.rivera.2010.362">Rivera et al 2010</a>].</p><p><b>Metabolic derangements.</b> In addition to elevated MMA, the majority of affected children develop lactic acidosis that can be severe and life threatening. Hypoglycemia was occasionally reported.</p><p><b>Others.</b> Other, less frequent, manifestations include hyperhidrosis, hypothermia, sleeping disturbance, rhabdomyolysis, and joint contractures.</p><p><b>Prognosis.</b> Life span is shortened, with median survival of 20 months. Two thirds (14/21) of affected children died during childhood – five in the neonatal period and nine during infancy and early childhood [<a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p></div><div id="suclg1-mtddepl.GenotypePhenotype_Correla"><h3>Genotype-Phenotype Correlations</h3><p>Pathogenic <i>SUCLG1</i> missense variants can result in some residual enzyme activity, and hence a milder phenotype. Survival in children with biallelic pathogenic missense variants was longer (median age: 18 months) than in children with biallelic loss-of-function variants (splice site, frameshift, and nonsense variants) (median age: birth) [<a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p></div><div id="suclg1-mtddepl.Nomenclature"><h3>Nomenclature</h3><p>Succinyl-CoA ligase deficiency can result from either biallelic pathogenic variants in <i>SUCLG1</i> (<i>SUCLG1</i>-related mtDNA depletion syndrome) or biallelic pathogenic variants in <i>SUCLA2</i> (<a href="/books/n/gene/sucla2-def/?report=reader"><i>SUCLA2</i>-related mtDNA depletion syndrome</a>).</p></div><div id="suclg1-mtddepl.Prevalence"><h3>Prevalence</h3><p><i>SUCLG1</i>-related mtDNA depletion syndrome is rare; the exact prevalence is unknown. To date 29 individuals with <i>SUCLG1</i>-related mtDNA depletion have been reported in families of different ethnic origins [<a class="bibr" href="#suclg1-mtddepl.REF.ostergaard.2007.383" rid="suclg1-mtddepl.REF.ostergaard.2007.383">Ostergaard et al 2007</a>, <a class="bibr" href="#suclg1-mtddepl.REF.ostergaard.2010.201" rid="suclg1-mtddepl.REF.ostergaard.2010.201">Ostergaard et al 2010</a>, <a class="bibr" href="#suclg1-mtddepl.REF.rivera.2010.362" rid="suclg1-mtddepl.REF.rivera.2010.362">Rivera et al 2010</a>, <a class="bibr" href="#suclg1-mtddepl.REF.rouzier.2010.670" rid="suclg1-mtddepl.REF.rouzier.2010.670">Rouzier et al 2010</a>, <a class="bibr" href="#suclg1-mtddepl.REF.valayannopoulos.2010.335" rid="suclg1-mtddepl.REF.valayannopoulos.2010.335">Valayannopoulos et al 2010</a>, <a class="bibr" href="#suclg1-mtddepl.REF.van_hove.2010.159" rid="suclg1-mtddepl.REF.van_hove.2010.159">Van Hove et al 2010</a>, <a class="bibr" href="#suclg1-mtddepl.REF.randolph.2011.149" rid="suclg1-mtddepl.REF.randolph.2011.149">Randolph et al 2011</a>, <a class="bibr" href="#suclg1-mtddepl.REF.sakamoto.2011.921" rid="suclg1-mtddepl.REF.sakamoto.2011.921">Sakamoto et al 2011</a>, <a class="bibr" href="#suclg1-mtddepl.REF.honzik.2012.749" rid="suclg1-mtddepl.REF.honzik.2012.749">Honzik et al 2012</a>, <a class="bibr" href="#suclg1-mtddepl.REF.navarrosastre.2012.409" rid="suclg1-mtddepl.REF.navarrosastre.2012.409">Navarro-Sastre et al 2012</a>, <a class="bibr" href="#suclg1-mtddepl.REF.landsverk.2014" rid="suclg1-mtddepl.REF.landsverk.2014">Landsverk et al 2014</a>, <a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>, <a class="bibr" href="#suclg1-mtddepl.REF.chu.2016.264" rid="suclg1-mtddepl.REF.chu.2016.264">Chu et al 2016</a>, <a class="bibr" href="#suclg1-mtddepl.REF.donti.2016.68" rid="suclg1-mtddepl.REF.donti.2016.68">Donti et al 2016</a>, <a class="bibr" href="#suclg1-mtddepl.REF.liu.2016.61" rid="suclg1-mtddepl.REF.liu.2016.61">Liu et al 2016</a>, <a class="bibr" href="#suclg1-mtddepl.REF.pupavac.2016.363" rid="suclg1-mtddepl.REF.pupavac.2016.363">Pupavac et al 2016</a>].</p></div></div><div id="suclg1-mtddepl.Genetically_Related_Allel"><h2 id="_suclg1-mtddepl_Genetically_Related_Allel_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with pathogenic variants in <i>SUCLG1</i>.</p></div><div id="suclg1-mtddepl.Differential_Diagnosis"><h2 id="_suclg1-mtddepl_Differential_Diagnosis_">Differential Diagnosis</h2><p><i>SUCLG1</i>-related mtDNA depletion syndrome needs to be differentiated from other mtDNA depletion syndromes, a genetically and clinically heterogeneous group of autosomal recessive disorders that are characterized by a severe reduction in mtDNA content leading to impaired energy production in affected tissues and organs. <a href="/books/NBK425223/table/suclg1-mtddepl.T.mitochondrial_dna_deple/?report=objectonly" target="object" rid-ob="figobsuclg1mtddeplTmitochondrialdnadeple">Table 3</a> includes the currently known mtDNA depletion syndromes.</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 (e.g., <i>TK2</i>, <i>SUCLA2</i>, <i>SUCLG1</i>, <i>RRM2B</i>, <i>DGUOK</i>, and <i>TYMP</i>) or mtDNA replication (e.g., <i>POLG</i> and <i>TWNK</i> [<i>C10orf2</i>]). The function of <i>FBXL4</i> is not yet known.</p><p>Mitochondrial DNA depletion syndromes are phenotypically classified into hepatocerebral, encephalomyopathic, neurogastrointestinal, and myopathic forms [<a class="bibr" href="#suclg1-mtddepl.REF.elhattab.2013.186" rid="suclg1-mtddepl.REF.elhattab.2013.186">El-Hattab & Scaglia 2013</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsuclg1mtddeplTmitochondrialdnadeple"><a href="/books/NBK425223/table/suclg1-mtddepl.T.mitochondrial_dna_deple/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobsuclg1mtddeplTmitochondrialdnadeple"><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="suclg1-mtddepl.T.mitochondrial_dna_deple"><a href="/books/NBK425223/table/suclg1-mtddepl.T.mitochondrial_dna_deple/?report=objectonly" target="object" rid-ob="figobsuclg1mtddeplTmitochondrialdnadeple">Table 3. </a></h4><p class="float-caption no_bottom_margin">Mitochondrial DNA Depletion Syndromes </p></div></div><p>Among mtDNA depletion syndromes, methylmalonic acid (MMA) is elevated only in <i>SUCLG1</i>- and <i>SUCLA2</i>-related mtDNA depletion syndromes.</p><p>The phenotypes of <i>SUCLG1</i>-related mtDNA depletion syndrome and <i>SUCLA2</i>-related mtDNA depletion syndrome may be difficult to be differentiate (see <a href="/books/NBK425223/table/suclg1-mtddepl.T.comparison_of_the_pheno/?report=objectonly" target="object" rid-ob="figobsuclg1mtddeplTcomparisonofthepheno">Table 4</a>).</p><p><i>SUCLA2</i>-related mtDNA depletion syndrome is characterized by onset of the following features in infancy or childhood: psychomotor retardation, hypotonia, dystonia, muscular atrophy, sensorineural hearing impairment, postnatal growth retardation, and feeding difficulties. Other, less frequent, features include distinctive facial features, contractures, kyphoscoliosis, gastroesophageal reflux, ptosis, choreoathetosis, ophthalmoplegia, and epilepsy. Of note, hepatopathy and cardiomyopathy, which have been reported in <i>SUCLG1</i>-related mtDNA depletion syndrome, have not been described in <i>SUCLA2</i>-related mtDNA depletion syndrome [<a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al 2016</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsuclg1mtddeplTcomparisonofthepheno"><a href="/books/NBK425223/table/suclg1-mtddepl.T.comparison_of_the_pheno/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobsuclg1mtddeplTcomparisonofthepheno"><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="suclg1-mtddepl.T.comparison_of_the_pheno"><a href="/books/NBK425223/table/suclg1-mtddepl.T.comparison_of_the_pheno/?report=objectonly" target="object" rid-ob="figobsuclg1mtddeplTcomparisonofthepheno">Table 4. </a></h4><p class="float-caption no_bottom_margin">Comparison of the Phenotypes of <i>SUCLG1</i>-Related mtDNA Depletion Syndrome and <i>SUCLA2</i>-Related mtDNA Deletion Syndromes </p></div></div></div><div id="suclg1-mtddepl.Management"><h2 id="_suclg1-mtddepl_Management_">Management</h2><div id="suclg1-mtddepl.Evaluations_Following_Ini"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>SUCLG1</i>-related mtDNA depletion syndrome the following evaluations are recommended:</p><ul><li class="half_rhythm"><div>Comprehensive neurologic examination and developmental/cognitive assessment. The following diagnostic modalities can be considered to assess the degree of neurologic involvement:</div><ul><li class="half_rhythm"><div>Brain MRI (if not performed during the diagnostic evaluation) to establish the degree of central nervous system involvement</div></li><li class="half_rhythm"><div>EEG if seizures are suspected</div></li></ul></li><li class="half_rhythm"><div>Echocardiogram to assess for cardiomyopathy</div></li><li class="half_rhythm"><div>Liver function tests including transaminases, albumin, total and direct bilirubin, and coagulation profile</div></li><li class="half_rhythm"><div>Audiologic evaluation</div></li><li class="half_rhythm"><div>Ophthalmologic examination for evidence of ptosis and/or strabismus</div></li><li class="half_rhythm"><div>Nutritional evaluation and swallowing assessment for feeding difficulties and growth failure</div></li><li class="half_rhythm"><div>Consultation with a clinical geneticist and/or genetic counselor</div></li></ul></div><div id="suclg1-mtddepl.Treatment_of_Manifestatio"><h3>Treatment of Manifestations</h3><p>Management is best provided by a multidisciplinary team including specialists in neurology, audiology, child development, gastroenterology, cardiology, nutrition, and clinical genetics. Treatments include the following:</p><ul><li class="half_rhythm"><div>Physical therapy to help maintain muscle function and prevent joint contractures</div></li><li class="half_rhythm"><div>Standard treatment with anti-seizure medication for seizures</div></li><li class="half_rhythm"><div>Nutritional support by a dietitian and the use of a nasogastric tube or gastrostomy tube feedings to address feeding difficulties and failure to thrive</div></li><li class="half_rhythm"><div>Chest physiotherapy, aggressive antibiotic treatment of chest infections, and artificial ventilation (including assisted nasal ventilation or intubation and the use of a tracheostomy and ventilator) for respiratory insufficiency</div></li><li class="half_rhythm"><div>Hypertrophic cardiomyopathy and hepatopathy, when present, require standard management by cardiologists and hepatologists, respectively.</div></li></ul></div><div id="suclg1-mtddepl.Surveillance"><h3>Surveillance</h3><p>No clinical guidelines for surveillance are available.</p><p>The following evaluations are suggested, with frequency varying according to the needs of the child:</p><ul><li class="half_rhythm"><div>Developmental and neurologic assessment</div></li><li class="half_rhythm"><div>Nutritional and growth assessment</div></li><li class="half_rhythm"><div>Echocardiogram</div></li><li class="half_rhythm"><div>Liver function tests</div></li><li class="half_rhythm"><div>Hearing evaluation</div></li><li class="half_rhythm"><div>Ophthalmologic examination</div></li></ul></div><div id="suclg1-mtddepl.Evaluation_of_Relatives_a"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#suclg1-mtddepl.Related_Genetic_Counselin">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="suclg1-mtddepl.Therapies_Under_Investiga"><h3>Therapies Under Investigation</h3><p>A group of mtDNA depletion syndromes is caused by defects in genes encoding proteins involved in maintenance of the mitochondrial deoxyribonucleotide pool. Because in vitro experimental studies have demonstrated improved mtDNA content following deoxyribonucleotide supplementation, this could potentially be a treatment for some mtDNA depletion syndromes [<a class="bibr" href="#suclg1-mtddepl.REF.c_mara.2014.2459" rid="suclg1-mtddepl.REF.c_mara.2014.2459">Cámara et al 2014</a>].</p><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.</p></div></div><div id="suclg1-mtddepl.Genetic_Counseling"><h2 id="_suclg1-mtddepl_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="suclg1-mtddepl.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>SUCLG1</i>-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria is inherited in an autosomal recessive manner.</p></div><div id="suclg1-mtddepl.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 obligate heterozygotes (i.e., carriers of one <i>SUCLG1</i> pathogenic variant).</div></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>At conception, each sib of an affected individual has 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> Individuals with <i>SUCLG1</i>-related mtDNA depletion syndrome are not reported 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>SUCLG1</i> pathogenic variant.</p></div><div id="suclg1-mtddepl.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>SUCLG1</i> pathogenic variants in the family.</p></div><div id="suclg1-mtddepl.Related_Genetic_Counselin"><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, clarification of carrier status, 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></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bibr" href="#suclg1-mtddepl.REF.huang.2022.389" rid="suclg1-mtddepl.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="suclg1-mtddepl.Prenatal_Testing_and_Prei"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>SUCLG1</i> pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.</p></div></div><div id="suclg1-mtddepl.Resources"><h2 id="_suclg1-mtddepl_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>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="suclg1-mtddepl.Molecular_Genetics"><h2 id="_suclg1-mtddepl_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="figsuclg1mtddeplmolgenTA"><a href="/books/NBK425223/table/suclg1-mtddepl.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobsuclg1mtddeplmolgenTA"><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="suclg1-mtddepl.molgen.TA"><a href="/books/NBK425223/table/suclg1-mtddepl.molgen.TA/?report=objectonly" target="object" rid-ob="figobsuclg1mtddeplmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">SUCLG1-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="figsuclg1mtddeplmolgenTB"><a href="/books/NBK425223/table/suclg1-mtddepl.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobsuclg1mtddeplmolgenTB"><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="suclg1-mtddepl.molgen.TB"><a href="/books/NBK425223/table/suclg1-mtddepl.molgen.TB/?report=objectonly" target="object" rid-ob="figobsuclg1mtddeplmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria (View All in OMIM) </p></div></div><div id="suclg1-mtddepl.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>Succinyl-CoA ligase (SUCL) is a mitochondrial heterodimeric enzyme of the Krebs cycle that 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>. SUCL catalyzes the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP. When the alpha subunit forms a heterodimer with <i>SUCLA2</i>-encoded beta subunits, the resulting SUCL enzyme utilizes ADP to generate ATP. In contrast, when the alpha subunit forms a heterodimer with <i>SUCLG2</i>-encoded beta subunits, the resulting SUCL enzyme utilizes GDP to generate GTP.</p><p>SUCL also forms a complex with the mitochondrial nucleoside diphosphate kinase (see <b>Abnormal gene product</b>).</p><p><b>Gene structure.</b>
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<i>SUCLG1</i> contains nine exons (<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_003849.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_003849.3</a>).</p><p><b>Pathogenic variants.</b> The spectrum of reported <i>SUCLG1</i> pathogenic variants includes missense, splice site, frameshift deletion, and nonsense variants. Missense variants are the most common, accounting for about half of pathogenic variants.</p><p><b>Normal gene product.</b>
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<i>SUCLG1</i> encodes the succinyl-CoA ligase [ADP/GDP-forming] subunit alpha of SUCL, which has 346 amino acid residues (<a href="https://www.ncbi.nlm.nih.gov/protein/NP_003840.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_003840.2</a>).</p><p><b>Abnormal gene product.</b> Pathogenic <i>SUCLG1</i> variants lead to dysfunctional SUCL protein. As SUCL forms a complex with the mitochondrial nucleoside diphosphate kinase, the lack of this complex in SUCL deficiency can disturb the kinase function, resulting in decreased mitochondrial nucleotide synthesis and, therefore, decreased mtDNA synthesis leading to mtDNA depletion. In addition, because SUCL deficiency results in impaired conversion of succinyl-CoA to succinate, succinyl-CoA accumulates and is converted to methylmalonyl-CoA by methylmalonyl-CoA mutase, leading to the accumulation of methylmalonic acid (MMA) [<a class="bibr" href="#suclg1-mtddepl.REF.elhattab.2013.186" rid="suclg1-mtddepl.REF.elhattab.2013.186">El-Hattab & Scaglia 2013</a>].</p></div></div><div id="suclg1-mtddepl.Chapter_Notes"><h2 id="_suclg1-mtddepl_Chapter_Notes_">Chapter Notes</h2><div id="suclg1-mtddepl.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>30 March 2017 (bp) Review posted live</div></li><li class="half_rhythm"><div>20 October 2016 (aeh) Original submission</div></li></ul></div></div><div id="suclg1-mtddepl.References"><h2 id="_suclg1-mtddepl_References_">References</h2><div id="suclg1-mtddepl.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.c_mara.2014.2459">Cámara Y, González-Vioque E, Scarpelli M, Torres-Torronteras J, Caballero A, Hirano M, Martí R. Administration of deoxyribonucleosides or inhibition of their catabolism as a pharmacological approach for mitochondrial DNA depletion syndrome. <span><span class="ref-journal">Hum Mol Genet. </span>2014;<span class="ref-vol">23</span>:2459–67.</span> [<a href="/pmc/articles/PMC6281351/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6281351</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24362886" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24362886</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo R, Verrigni D, Rasmussen M, de Coo R, Amartino H, Bianchi M, Buhas D, Mesli S, Naess K, Born AP, Woldseth B, Prontera P, Batbayli M, Ravn K, Joensen F, Cordelli DM, Santorelli FM, Tulinius M, Darin N, Duno M, Jouvencel P, Burlina A, Stangoni G, Bertini E, Redonnet-Vernhet I, Wibrand F, Dionisi-Vici C, Uusimaa J, Vieira P, Osorio AN, McFarland R, Taylor RW, Holme E, Ostergaard E. Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1: phenotype and genotype correlations in 71 patients. <span><span class="ref-journal">J Inherit Metab Dis. </span>2016;<span class="ref-vol">39</span>:243–52.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26475597" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26475597</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.chu.2016.264">Chu J, Pupavac M, Watkins D, Tian X, Feng Y, Chen S, Fenter R, Zhang VW, Wang J, Wong LJ, Rosenblatt DS. Next generation sequencing of patients with mut methylmalonic aciduria: Validation of somatic cell studies and identification of 16 novel mutations. <span><span class="ref-journal">Mol Genet Metab. </span>2016;<span class="ref-vol">118</span>:264–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27233228" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27233228</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.donti.2016.68">Donti TR, Masand R, Scott DA, Craigen WJ, Graham BH. Expanding the phenotypic spectrum of Succinyl-CoA ligase deficiency through functional validation of a new SUCLG1 variant. <span><span class="ref-journal">Mol Genet Metab. </span>2016;<span class="ref-vol">119</span>:68–74.</span> [<a href="/pmc/articles/PMC5031536/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5031536</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27484306" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27484306</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.elhattab.2013.186">El-Hattab AW, Scaglia F. Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options. <span><span class="ref-journal">Neurotherapeutics. </span>2013;<span class="ref-vol">10</span>:186–98.</span> [<a href="/pmc/articles/PMC3625391/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3625391</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23385875" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23385875</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.honzik.2012.749">Honzik T, Tesarova M, Magner M, Mayr J, Jesina P, Vesela K, Wenchich L, Szentivanyi K, Hansikova H, Sperl W, Zeman J. Neonatal onset of mitochondrial disorders in 129 patients: clinical and laboratory characteristics and a new approach to diagnosis. <span><span class="ref-journal">J Inherit Metab Dis. </span>2012;<span class="ref-vol">35</span>:749–59.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22231385" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22231385</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.huang.2022.389">Huang SJ, Amendola LM, Sternen DL. Variation among DNA banking consent forms: points for clinicians to bank on. <span><span class="ref-journal">J Community Genet. </span>2022;<span class="ref-vol">13</span>:389–97.</span> [<a href="/pmc/articles/PMC9314484/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9314484</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35834113" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35834113</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.landsverk.2014">Landsverk ML, Zhang VW, Wong LC, Andersson HC. A SUCLG1 mutation in a patient with mitochondrial DNA depletion and congenital anomalies. Mol Genet Metab Rep. 2014;1:451-4. eCollection 2014. [<a href="/pmc/articles/PMC5121340/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5121340</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27896121" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27896121</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.liu.2016.61">Liu Y, Li X, Wang Q, Ding Y, Song J, Yang Y. Five novel SUCLG1 mutations in three Chinese patients with succinate-CoA ligase deficiency noticed by mild methylmalonic aciduria. <span><span class="ref-journal">Brain Dev. </span>2016;<span class="ref-vol">38</span>:61–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26028457" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26028457</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.navarrosastre.2012.409">Navarro-Sastre A, Tort F, Garcia-Villoria J, Pons MR, Nascimento A, Colomer J, Campistol J, Yoldi ME, López-Gallardo E, Montoya J, Unceta M, Martinez MJ, Briones P, Ribes A. Mitochondrial DNA depletion syndrome: new descriptions and the use of citrate synthase as a helpful tool to better characterise the patients. <span><span class="ref-journal">Mol Genet Metab. </span>2012;<span class="ref-vol">107</span>:409–15.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22980518" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22980518</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.ostergaard.2007.383">Ostergaard E, Christensen E, Kristensen E, Mogensen B, Duno M, Shoubridge EA, Wibrand F. Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. <span><span class="ref-journal">Am J Hum Genet. </span>2007;<span class="ref-vol">81</span>:383–7.</span> [<a href="/pmc/articles/PMC1950792/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1950792</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17668387" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17668387</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.ostergaard.2010.201">Ostergaard E, Schwartz M, Batbayli M, Christensen E, Hjalmarson O, Kollberg G, Holme E. A novel missense mutation in SUCLG1 associated with mitochondrial DNA depletion, encephalomyopathic form, with methylmalonic aciduria. <span><span class="ref-journal">Eur J Pediatr. </span>2010;<span class="ref-vol">169</span>:201–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19526370" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19526370</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.pupavac.2016.363">Pupavac M, Tian X, Chu J, Wang G, Feng Y, Chen S, Fenter R, Zhang VW, Wang J, Watkins D, Wong LJ, Rosenblatt DS. Added value of next generation gene panel analysis for patients with elevated methylmalonic acid and no clinical diagnosis following functional studies of vitamin B12 metabolism. <span><span class="ref-journal">Mol Genet Metab. </span>2016;<span class="ref-vol">117</span>:363–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26827111" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26827111</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.randolph.2011.149">Randolph LM, Jackson HA, Wang J, Shimada H, Sanchez-Lara PA, Wong DA, Wong LJ, Boles RG. Fatal infantile lactic acidosis and a novel homozygous mutation in the SUCLG1 gene: a mitochondrial DNA depletion disorder. <span><span class="ref-journal">Mol Genet Metab. </span>2011;<span class="ref-vol">102</span>:149–52.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21093335" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21093335</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.richards.2015.405">Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. <span><span class="ref-journal">Genet Med. </span>2015;<span class="ref-vol">17</span>:405–24.</span> [<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.rivera.2010.362">Rivera H, Merinero B, Martinez-Pardo M, Arroyo I, Ruiz-Sala P, Bornstein B, Serra-Suhe C, Gallardo E, Marti R, Moran MJ, Ugalde C, Perez-Jurado LA, Andreu AL, Garesse R, Ugarte M, Arenas J, Martin MA. Marked mitochondrial DNA depletion associated with a novel SUCLG1 gene mutation resulting in lethal neonatal acidosis, multi-organ failure, and interrupted aortic arch. <span><span class="ref-journal">Mitochondrion. </span>2010;<span class="ref-vol">10</span>:362–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20227526" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20227526</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.rouzier.2010.670">Rouzier C, Le Guédard-Méreuze S, Fragaki K, Serre V, Miro J, Tuffery-Giraud S, Chaussenot A, Bannwarth S, Caruba C, Ostergaard E, Pellissier JF, Richelme C, Espil C, Chabrol B, Paquis-Flucklinger V. The severity of phenotype linked to SUCLG1 mutations could be correlated with residual amount of SUCLG1 protein. <span><span class="ref-journal">J Med Genet. </span>2010;<span class="ref-vol">47</span>:670–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20693550" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20693550</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.sakamoto.2011.921">Sakamoto O, Ohura T, Murayama K, Ohtake A, Harashima H, Abukawa D, Takeyama J, Haginoya K, Miyabayashi S, Kure S. Neonatal lactic acidosis with methylmalonic aciduria due to novel mutations in the SUCLG1 gene. <span><span class="ref-journal">Pediatr Int. </span>2011;<span class="ref-vol">53</span>:921–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21639866" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21639866</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.valayannopoulos.2010.335">Valayannopoulos V, Haudry C, Serre V, Barth M, Boddaert N, Arnoux JB, Cormier-Daire V, Rio M, Rabier D, Vassault A, Munnich A, Bonnefont JP, de Lonlay P, Rötig A, Lebre AS. New SUCLG1 patients expanding the phenotypic spectrum of this rare cause of mild methylmalonic aciduria. <span><span class="ref-journal">Mitochondrion. </span>2010;<span class="ref-vol">10</span>:335–41.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20197121" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20197121</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="suclg1-mtddepl.REF.van_hove.2010.159">Van Hove JL, Saenz MS, Thomas JA, Gallagher RC, Lovell MA, Fenton LZ, Shanske S, Myers SM, Wanders RJ, Ruiter J, Turkenburg M, Waterham HR. Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathy. <span><span class="ref-journal">Pediatr Res. </span>2010;<span class="ref-vol">68</span>:159–64.</span> [<a href="/pmc/articles/PMC2928220/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2928220</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20453710" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20453710</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK425223_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">Associate 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">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">March 30, 2017</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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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. SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria. 2017 Mar 30. 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/sucla2-def/?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/syne1ca-ar/?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="figobsuclg1mtddeplTmoleculargenetictesti"><div id="suclg1-mtddepl.T.molecular_genetic_testi" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>SUCLG1</i>-Related mtDNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK425223/table/suclg1-mtddepl.T.molecular_genetic_testi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__suclg1-mtddepl.T.molecular_genetic_testi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_suclg1-mtddepl.T.molecular_genetic_testi_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_suclg1-mtddepl.T.molecular_genetic_testi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_suclg1-mtddepl.T.molecular_genetic_testi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_suclg1-mtddepl.T.molecular_genetic_testi_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SUCLG1</i>
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</td><td headers="hd_h_suclg1-mtddepl.T.molecular_genetic_testi_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_suclg1-mtddepl.T.molecular_genetic_testi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">21/21 <sup>4</sup></td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.molecular_genetic_testi_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_suclg1-mtddepl.T.molecular_genetic_testi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported to date <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="suclg1-mtddepl.TF.1.1"><p class="no_margin">See <a href="/books/NBK425223/?report=reader#suclg1-mtddepl.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="suclg1-mtddepl.TF.1.2"><p class="no_margin">See <a href="#suclg1-mtddepl.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="suclg1-mtddepl.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 small intragenic deletions/insertions and missense, nonsense, and splice site variants; 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="suclg1-mtddepl.TF.1.4"><p class="no_margin">
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<a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al [2016]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="suclg1-mtddepl.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.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsuclg1mtddeplTclinicalmanifestations"><div id="suclg1-mtddepl.T.clinical_manifestations" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Clinical Manifestations of <i>SUCLG1</i>-Related mtDNA Depletion Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK425223/table/suclg1-mtddepl.T.clinical_manifestations/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__suclg1-mtddepl.T.clinical_manifestations_lrgtbl__"><table><thead><tr><th id="hd_h_suclg1-mtddepl.T.clinical_manifestations_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Frequency</th><th id="hd_h_suclg1-mtddepl.T.clinical_manifestations_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Manifestations</th></tr></thead><tbody><tr><td headers="hd_h_suclg1-mtddepl.T.clinical_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>50%</td><td headers="hd_h_suclg1-mtddepl.T.clinical_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>Developmental delay & cognitive impairment</div></li><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Muscle atrophy</div></li><li class="half_rhythm"><div>Feeding difficulties</div></li><li class="half_rhythm"><div>Lactic acidosis</div></li></ul>
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</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.clinical_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20%-50%</td><td headers="hd_h_suclg1-mtddepl.T.clinical_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>Growth retardation / failure to thrive</div></li><li class="half_rhythm"><div>Hepatopathy</div></li><li class="half_rhythm"><div>Sensorineural hearing impairment</div></li><li class="half_rhythm"><div>Dystonia</div></li><li class="half_rhythm"><div>Hypertonia</div></li></ul>
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</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.clinical_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><20%</td><td headers="hd_h_suclg1-mtddepl.T.clinical_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>Hypertrophic cardiomyopathy</div></li><li class="half_rhythm"><div>Recurrent respiratory infections</div></li><li class="half_rhythm"><div>Respiratory distress</div></li><li class="half_rhythm"><div>Apnea</div></li><li class="half_rhythm"><div>Recurrent vomiting</div></li><li class="half_rhythm"><div>Gastroesophageal reflux disease</div></li><li class="half_rhythm"><div>Ptosis</div></li><li class="half_rhythm"><div>Strabismus</div></li><li class="half_rhythm"><div>Epilepsy</div></li><li class="half_rhythm"><div>Myoclonus</div></li><li class="half_rhythm"><div>Microcephaly</div></li><li class="half_rhythm"><div>Choreoathetosis</div></li><li class="half_rhythm"><div>Hyperhidrosis</div></li><li class="half_rhythm"><div>Sleep disturbance</div></li><li class="half_rhythm"><div>Rhabdomyolysis</div></li><li class="half_rhythm"><div>Contractures</div></li><li class="half_rhythm"><div>Hypothermia</div></li><li class="half_rhythm"><div>Hypoglycemia</div></li></ul>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobsuclg1mtddeplTmitochondrialdnadeple"><div id="suclg1-mtddepl.T.mitochondrial_dna_deple" 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/NBK425223/table/suclg1-mtddepl.T.mitochondrial_dna_deple/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__suclg1-mtddepl.T.mitochondrial_dna_deple_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mitochondrial DNA Depletion Syndrome #, Type</th><th id="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference <sup>2</sup></th></tr></thead><tbody><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_1" rowspan="5" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Hepato-cerebral</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3, hepatocerebral type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4A, Alpers type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/alpers/?report=reader"><i>POLG</i>-Related Disorders</a>
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</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6, hepatocerebral type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/mpv17-mtdep/?report=reader"><i>MPV17</i>-Related Hepatocerebral mtDNA Depletion Syndrome</a>
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</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><i>TWNK</i> (<i>C10orf2</i>)</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7, hepatocerebral type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/271245" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">271245</a></td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15, hepatocerebral type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/617156" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617156</a></td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_1" rowspan="6" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Encephalo-<br />myopathic</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_2" rowspan="1" 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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5, encephalomyopathic type w/methylmalonic aciduria</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/sucla2-def/?report=reader"><i>SUCLA2</i>-Related mtDNA Depletion Syndrome, Encephalomyopathic Form w/Methylmalonic Aciduria</a>
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</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<i>FBXL4</i>
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</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13, encephalomyopathic type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/fbxl4-mtddepl/?report=reader"><i>FBXL4</i>-Related Encephalomyopathic mtDNA Depletion Syndrome</a>
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</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">9, encephalomyopathic type w/methylmalonic aciduria</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SUCLG1</i>-Related mtDNA Depletion Syndrome, Encephalomyopathic Form w/Methylmalonic Aciduria</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8A, encephalomyopathic type w/renal tubulopathy</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" 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>-Related Mitochondrial Disease</a>
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</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">14, encephalocardiomyopathic type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/616896" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616896</a></td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Encephalomyopathic type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/613163" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">613163</a></td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Neurogastro-<br />intestinal</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1, MNGIE type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/mngie/?report=reader">Mitochondrial Neurogastrointestinal Encephalopathy Disease</a>
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</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4B, MNGIE type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/alpers/?report=reader"><i>POLG</i>-Related Disorders</a>
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</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8B, MNGIE type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" 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>-Related Mitochondrial Disease</a>
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</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">Myopathic</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2, myopathic type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/tk2-mtddepl/?report=reader"><i>TK2</i>-Related mtDNA Depletion Syndrome, Myopathic Form</a>
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</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10, cardiomyopathic type (Sengers syndrome)</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/212350" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">212350</a></td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">11, myopathic type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/615084" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">615084</a></td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_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_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12B, cardiomyopathic type</td><td headers="hd_h_suclg1-mtddepl.T.mitochondrial_dna_deple_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/615418" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">615418</a></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="suclg1-mtddepl.TF.3.1"><p class="no_margin">Within each phenotypic category, mtDNA depletion syndromes are ordered by relative prevalence.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="suclg1-mtddepl.TF.3.2"><p class="no_margin">See hyperlinked <i>GeneReview</i> or OMIM phenotype entry for more information.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsuclg1mtddeplTcomparisonofthepheno"><div id="suclg1-mtddepl.T.comparison_of_the_pheno" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Comparison of the Phenotypes of <i>SUCLG1</i>-Related mtDNA Depletion Syndrome and <i>SUCLA2</i>-Related mtDNA Deletion Syndromes</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK425223/table/suclg1-mtddepl.T.comparison_of_the_pheno/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__suclg1-mtddepl.T.comparison_of_the_pheno_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;"></th><th id="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Mitochondrial DNA Depletion Syndrome</th></tr><tr><th headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1" id="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical Finding</th><th headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2" id="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SUCLG1</i>-Related</th><th headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2" id="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SUCLA2</i>-Related</th></tr></thead><tbody><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Age at onset</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Majority present at birth</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy or childhood</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Median survival</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20 months</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20 years</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Developmental delay</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>50%</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>75%</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypotonia</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>50%</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>75%</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Muscular atrophy</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>50%</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25%-50%</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Feeding problems</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Equally common</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Failure to thrive</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Equally common</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Liver involvement</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">40%</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not reported</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hearing impairment</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20%-50%</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>75%</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Dystonia</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25%-50%</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>75%</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypertonia</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25%-50%</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><20%</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypertrophic cardiomyopathy</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">14%</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not reported</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">On brain MRI:</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Basal ganglia hyperintensities</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">80%</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">70%</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Cerebral atrophy</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30%</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">70%</td></tr><tr><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_1 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Leukoencephalopathy</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20%</td><td headers="hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_1_2 hd_h_suclg1-mtddepl.T.comparison_of_the_pheno_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15%</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">
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<a class="bibr" href="#suclg1-mtddepl.REF.carrozzo.2016.243" rid="suclg1-mtddepl.REF.carrozzo.2016.243">Carrozzo et al [2016]</a>
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</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsuclg1mtddeplmolgenTA"><div id="suclg1-mtddepl.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>SUCLG1-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/NBK425223/table/suclg1-mtddepl.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__suclg1-mtddepl.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_suclg1-mtddepl.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_suclg1-mtddepl.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_suclg1-mtddepl.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_suclg1-mtddepl.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_suclg1-mtddepl.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_suclg1-mtddepl.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_suclg1-mtddepl.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/8802" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>SUCLG1</i>
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</a>
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</td><td headers="hd_b_suclg1-mtddepl.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=8802" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">2p11<wbr style="display:inline-block"></wbr>​.2</a>
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</td><td headers="hd_b_suclg1-mtddepl.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/P53597" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Succinate--CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial</a>
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</td><td headers="hd_b_suclg1-mtddepl.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/SUCLG1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SUCLG1 database</a>
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</td><td headers="hd_b_suclg1-mtddepl.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=SUCLG1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SUCLG1</a>
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</td><td headers="hd_b_suclg1-mtddepl.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=SUCLG1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SUCLG1</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="suclg1-mtddepl.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="figobsuclg1mtddeplmolgenTB"><div id="suclg1-mtddepl.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria (<a href="/omim/245400,611224" 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/NBK425223/table/suclg1-mtddepl.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__suclg1-mtddepl.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/245400" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">245400</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MITOCHONDRIAL DNA DEPLETION SYNDROME 9 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA); MTDPS9</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/611224" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">611224</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SUCCINATE-CoA LIGASE, GDP/ADP-FORMING, SUBUNIT ALPHA; SUCLG1</td></tr></tbody></table></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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