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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>MPV17-Related Mitochondrial DNA Maintenance Defect - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="MPV17-Related Mitochondrial DNA Maintenance Defect">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2018/05/17">
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<meta name="citation_author" content="Ayman W El-Hattab">
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<meta name="citation_author" content="Julia Wang">
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<meta name="citation_author" content="Hongzheng Dai">
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<meta name="citation_author" content="Mohammed Almannai">
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<meta name="citation_author" content="Fernando Scaglia">
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<meta name="citation_author" content="William J Craigen">
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<meta name="citation_author" content="Lee-Jun C Wong">
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<meta name="citation_pmid" content="22593919">
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<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK92947/">
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<meta name="citation_keywords" content="Mitochondrial DNA Depletion Syndrome 6 (MTDPS6), Hepatocerebral Type">
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<meta name="citation_keywords" content="MPV17 Deficiency">
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<meta name="citation_keywords" content="MPV17 Hepatocerebral Mitochondrial DNA Depletion Syndrome">
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<meta name="citation_keywords" content="Mitochondrial DNA Depletion Syndrome 6 (MTDPS6), Hepatocerebral Type">
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<meta name="citation_keywords" content="MPV17 Deficiency">
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<meta name="citation_keywords" content="MPV17 Hepatocerebral Mitochondrial DNA Depletion Syndrome">
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<meta name="citation_keywords" content="MPV17-Related Encephalohepatopathy, Including Navajo Neurohepatopathy">
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<meta name="citation_keywords" content="MPV17-Related Neuromyopathy">
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<meta name="citation_keywords" content="Mitochondrial inner membrane protein Mpv17">
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<meta name="citation_keywords" content="MPV17">
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<meta name="citation_keywords" content="MPV17-Related Mitochondrial DNA Maintenance Defect">
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<meta name="DC.Title" content="MPV17-Related Mitochondrial DNA Maintenance Defect">
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<meta name="DC.Type" content="Text">
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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="Julia Wang">
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<meta name="DC.Contributor" content="Hongzheng Dai">
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<meta name="DC.Contributor" content="Mohammed Almannai">
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<meta name="DC.Contributor" content="Fernando Scaglia">
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<meta name="DC.Contributor" content="William J Craigen">
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<meta name="DC.Contributor" content="Lee-Jun C Wong">
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<meta name="DC.Date" content="2018/05/17">
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<meta name="description" content="MPV17-related mitochondrial DNA (mtDNA) maintenance defect presents in the vast majority of affected individuals as an early-onset encephalohepatopathic (hepatocerebral) disease that is typically associated with mtDNA depletion, particularly in the liver. A later-onset neuromyopathic disease characterized by myopathy and neuropathy, and associated with multiple mtDNA deletions in muscle, has also rarely been described. MPV17-related mtDNA maintenance defect, encephalohepatopathic form is characterized by:">
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<meta name="og:description" content="MPV17-related mitochondrial DNA (mtDNA) maintenance defect presents in the vast majority of affected individuals as an early-onset encephalohepatopathic (hepatocerebral) disease that is typically associated with mtDNA depletion, particularly in the liver. A later-onset neuromyopathic disease characterized by myopathy and neuropathy, and associated with multiple mtDNA deletions in muscle, has also rarely been described. MPV17-related mtDNA maintenance defect, encephalohepatopathic form is characterized by:">
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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="_NBK92947_"><span class="title" itemprop="name"><i>MPV17-</i>Related Mitochondrial DNA Maintenance Defect</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: Mitochondrial DNA Depletion Syndrome 6 (MTDPS6), Hepatocerebral Type; MPV17 Deficiency; <i>MPV17</i> Hepatocerebral Mitochondrial DNA Depletion Syndrome</div><p class="contribs">El-Hattab AW, Wang J, Dai H, et al.</p><p class="fm-aai"><a href="#_NBK92947_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 19 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="mpv17-mtdep.Summary" itemprop="description"><h2 id="_mpv17-mtdep_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>MPV17</i>-related mitochondrial DNA (mtDNA) maintenance defect presents in the vast majority of affected individuals as an early-onset encephalohepatopathic (hepatocerebral) disease that is typically associated with mtDNA depletion, particularly in the liver. A later-onset neuromyopathic disease characterized by myopathy and neuropathy, and associated with multiple mtDNA deletions in muscle, has also rarely been described. <i>MPV17</i>-related mtDNA maintenance defect, encephalohepatopathic form is characterized by:</p><ul><li class="half_rhythm"><div>Hepatic manifestations (liver dysfunction that typically progresses to liver failure, cholestasis, hepatomegaly, and steatosis);</div></li><li class="half_rhythm"><div>Neurologic involvement (developmental delay, hypotonia, microcephaly, and motor and sensory peripheral neuropathy);</div></li><li class="half_rhythm"><div>Gastrointestinal manifestations (gastrointestinal dysmotility, feeding difficulties, and failure to thrive); and</div></li><li class="half_rhythm"><div>Metabolic derangements (lactic acidosis and hypoglycemia).</div></li></ul><p>Less frequent manifestations include renal tubulopathy, nephrocalcinosis, and hypoparathyroidism. Progressive liver disease often leads to death in infancy or early childhood. Hepatocellular carcinoma has been reported.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>MPV17</i>-related mtDNA maintenance defect is established in a proband by the identification of biallelic pathogenic variants in <i>MPV17</i> by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Ideally management is by a multidisciplinary team including specialists in hepatology, neurology, nutrition, clinical genetics, and child development. Nutritional support should be provided by a dietitian experienced in managing children with liver diseases; prevention of hypoglycemia requires frequent feeds and uncooked cornstarch (1-2 g/kg/dose). Although liver transplantation remains the only treatment option for liver failure, it is controversial because of the multisystem involvement in this disorder.</p><p><i>Prevention of secondary complications:</i> Prevent nutritional deficiencies (e.g., of fat-soluble vitamins) by ensuring adequate intake.</p><p><i>Surveillance:</i> Monitor:</p><ul><li class="half_rhythm"><div>Liver function to assess progression of liver disease;</div></li><li class="half_rhythm"><div>Serum alpha fetoprotein (AFP) concentration and hepatic ultrasound examination for evidence of hepatocellular carcinoma;</div></li><li class="half_rhythm"><div>Development, neurologic status, and nutritional status.</div></li></ul><p><i>Agents/circumstances to avoid:</i> Prolonged fasting.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>MPV17</i>-related mtDNA maintenance defect is inherited in an autosomal recessive manner. 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. Carrier testing for at-risk relatives and prenatal testing for a pregnancy at increased risk are possible if the pathogenic variants in the family are known.</p></div></div><div id="mpv17-mtdep.GeneReview_Scope"><h2 id="_mpv17-mtdep_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmpv17mtdepTd"><a href="/books/NBK92947/table/mpv17-mtdep.Td/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobmpv17mtdepTd"><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="mpv17-mtdep.Td"><a href="/books/NBK92947/table/mpv17-mtdep.Td/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTd">Table</a></h4><p class="float-caption no_bottom_margin"><i>MPV17</i>-related encephalohepatopathy, including Navajo neurohepatopathy <sup>2</sup> <i>MPV17</i>-related neuromyopathy</p></div></div></div><div id="mpv17-mtdep.Diagnosis"><h2 id="_mpv17-mtdep_Diagnosis_">Diagnosis</h2><div id="mpv17-mtdep.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>MPV17</i>-related mitochondrial DNA (mtDNA) maintenance defect <b>should be suspected</b> in individuals with the following clinical features, brain MRI findings, and supportive laboratory findings.</p><p>
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<b>Clinical features</b>
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</p><ul><li class="half_rhythm"><div>Hepatic</div><ul><li class="half_rhythm"><div>Liver dysfunction or failure</div></li><li class="half_rhythm"><div>Cholestasis and steatosis</div></li><li class="half_rhythm"><div>Hepatomegaly</div></li></ul></li><li class="half_rhythm"><div>Neurologic</div><ul><li class="half_rhythm"><div>Developmental delay</div></li><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Microcephaly</div></li><li class="half_rhythm"><div>Motor and sensory peripheral neuropathy</div></li></ul></li><li class="half_rhythm"><div>Gastrointestinal</div><ul><li class="half_rhythm"><div>Gastrointestinal dysmotility</div></li><li class="half_rhythm"><div>Feeding difficulties</div></li><li class="half_rhythm"><div>Failure to thrive</div></li></ul></li></ul><p>
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<b>Brain MRI findings</b>
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</p><ul><li class="half_rhythm"><div>White matter abnormalities</div></li><li class="half_rhythm"><div>Brain stem signal abnormalities</div></li><li class="half_rhythm"><div>Basal ganglia signal abnormalities</div></li></ul><p>
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<b>Supportive laboratory findings</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm">Serum testing</div><ul><li class="half_rhythm"><div>Elevated hepatic transaminases and hyperbilirubinemia</div></li><li class="half_rhythm"><div>Lactic acidosis</div></li><li class="half_rhythm"><div>Hypoglycemia</div></li></ul></li><li class="half_rhythm"><div class="half_rhythm">Liver histology</div><ul><li class="half_rhythm"><div>Steatosis</div></li><li class="half_rhythm"><div>Cirrhosis</div></li></ul></li><li class="half_rhythm"><div class="half_rhythm">Mitochondrial DNA analysis in liver and muscle [<a class="bibr" href="#mpv17-mtdep.REF.elhattab.2018.461" rid="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab et al 2018</a>]</div><ul><li class="half_rhythm"><div>Mitochondrial DNA content:</div><ul><li class="half_rhythm"><div>Is typically reduced in liver tissue (<20% of that found in tissue- and age-matched controls);</div></li><li class="half_rhythm"><div>Can also be reduced in muscle tissue (typically <30% of that found in tissue- and age-matched controls).</div></li></ul></li><li class="half_rhythm"><div>Multiple mtDNA deletions have been occasionally described in muscle and liver.</div></li></ul></li><li class="half_rhythm"><div class="half_rhythm">Electron transport chain (ETC) assays in liver and muscle tissue of affected individuals typically show decreased activity of multiple complexes with complex I having reduced activity in 80% of affected individuals [<a class="bibr" href="#mpv17-mtdep.REF.elhattab.2018.461" rid="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab et al 2018</a>].</div><div class="half_rhythm">Note: Neither mtDNA analysis nor ETC assays are required to make the diagnosis of <i>MPV17</i>-related mtDNA maintenance defect.</div></li></ul></div><div id="mpv17-mtdep.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>MPV17</i>-related mtDNA maintenance defect <b>is established</b> in a proband with biallelic pathogenic (or likely pathogenic) variants in <i>MPV17</i> by molecular genetic testing (see <a href="/books/NBK92947/table/mpv17-mtdep.T.molecular_genetic_testing/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmoleculargenetictesting">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bibr" href="#mpv17-mtdep.REF.richards.2015.405" rid="mpv17-mtdep.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of biallelic <i>MPV17</i> variants of uncertain significance (or of one known <i>MPV17</i> pathogenic variant and one <i>MPV17</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Because the phenotype of <i>MPV17</i>-related mtDNA maintenance defect is indistinguishable from many other inherited disorders with encephalohepatopathy, recommended molecular genetic testing approaches include use of a <b>multigene panel</b> or <b>comprehensive genomic testing</b>.</p><p>Note: Single-gene testing (sequence analysis of <i>MPV17</i>, followed by gene-targeted deletion/duplication analysis) is rarely useful.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> that includes <i>MPV17</i> and other genes of interest (see <a href="#mpv17-mtdep.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive genomic testing</b> (which does not require the clinician to determine which gene[s] are likely involved) is another good option. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</div><div class="half_rhythm">Exome array (when clinically available) may be considered if exome sequencing is not diagnostic, particularly when evidence supports autosomal dominant inheritance.</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></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmpv17mtdepTmoleculargenetictesting"><a href="/books/NBK92947/table/mpv17-mtdep.T.molecular_genetic_testing/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobmpv17mtdepTmoleculargenetictesting"><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="mpv17-mtdep.T.molecular_genetic_testing"><a href="/books/NBK92947/table/mpv17-mtdep.T.molecular_genetic_testing/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmoleculargenetictesting">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>MPV17</i>-Related mtDNA Maintenance Defect </p></div></div></div></div><div id="mpv17-mtdep.Clinical_Characteristics"><h2 id="_mpv17-mtdep_Clinical_Characteristics_">Clinical Characteristics</h2><div id="mpv17-mtdep.Clinical_Description"><h3>Clinical Description</h3><p><i>MPV17</i>-related mtDNA maintenance defect has been reported in 100 individuals [<a class="bibr" href="#mpv17-mtdep.REF.karadimas.2006.544" rid="mpv17-mtdep.REF.karadimas.2006.544">Karadimas et al 2006</a>, <a class="bibr" href="#mpv17-mtdep.REF.spinazzola.2006.570" rid="mpv17-mtdep.REF.spinazzola.2006.570">Spinazzola et al 2006</a>, <a class="bibr" href="#mpv17-mtdep.REF.wong.2007.1218" rid="mpv17-mtdep.REF.wong.2007.1218">Wong et al 2007</a>, <a class="bibr" href="#mpv17-mtdep.REF.navarrosastre.2008.234" rid="mpv17-mtdep.REF.navarrosastre.2008.234">Navarro-Sastre et al 2008</a>, <a class="bibr" href="#mpv17-mtdep.REF.spinazzola.2008.1108" rid="mpv17-mtdep.REF.spinazzola.2008.1108">Spinazzola et al 2008</a>, <a class="bibr" href="#mpv17-mtdep.REF.kaji.2009.292" rid="mpv17-mtdep.REF.kaji.2009.292">Kaji et al 2009</a>, <a class="bibr" href="#mpv17-mtdep.REF.parini.2009.215" rid="mpv17-mtdep.REF.parini.2009.215">Parini et al 2009</a>, <a class="bibr" href="#mpv17-mtdep.REF.elhattab.2010.300" rid="mpv17-mtdep.REF.elhattab.2010.300">El-Hattab et al 2010</a>, <a class="bibr" href="#mpv17-mtdep.REF.aljasmi.2011.529" rid="mpv17-mtdep.REF.aljasmi.2011.529">Al-Jasmi et al 2011</a>, <a class="bibr" href="#mpv17-mtdep.REF.alsaman.2012.285" rid="mpv17-mtdep.REF.alsaman.2012.285">AlSaman et al 2012</a>, <a class="bibr" href="#mpv17-mtdep.REF.blakely.2012.587" rid="mpv17-mtdep.REF.blakely.2012.587">Blakely et al 2012</a>, <a class="bibr" href="#mpv17-mtdep.REF.garone.2012.1648" rid="mpv17-mtdep.REF.garone.2012.1648">Garone et al 2012</a>, <a class="bibr" href="#mpv17-mtdep.REF.merkle.2012.e34" rid="mpv17-mtdep.REF.merkle.2012.e34">Merkle et al 2012</a>, <a class="bibr" href="#mpv17-mtdep.REF.nogueira.2012.764" rid="mpv17-mtdep.REF.nogueira.2012.764">Nogueira et al 2012</a>, <a class="bibr" href="#mpv17-mtdep.REF.alhussaini.2014" rid="mpv17-mtdep.REF.alhussaini.2014">Al-Hussaini et al 2014</a>, <a class="bibr" href="#mpv17-mtdep.REF.bijarniamahay.2014.666" rid="mpv17-mtdep.REF.bijarniamahay.2014.666">Bijarnia-Mahay et al 2014</a>, <a class="bibr" href="#mpv17-mtdep.REF.mendelsohn.2014.37" rid="mpv17-mtdep.REF.mendelsohn.2014.37">Mendelsohn et al 2014</a>, <a class="bibr" href="#mpv17-mtdep.REF.piekutowskaabramczuk.2014.573" rid="mpv17-mtdep.REF.piekutowskaabramczuk.2014.573">Piekutowska-Abramczuk et al 2014</a>, <a class="bibr" href="#mpv17-mtdep.REF.sarkhy.2014.175" rid="mpv17-mtdep.REF.sarkhy.2014.175">Sarkhy et al 2014</a>, <a class="bibr" href="#mpv17-mtdep.REF.uusimaa.2014.184" rid="mpv17-mtdep.REF.uusimaa.2014.184">Uusimaa et al 2014</a>, <a class="bibr" href="#mpv17-mtdep.REF.vilarinho.2014.1056" rid="mpv17-mtdep.REF.vilarinho.2014.1056">Vilarinho et al 2014</a>, <a class="bibr" href="#mpv17-mtdep.REF.choi.2015.179" rid="mpv17-mtdep.REF.choi.2015.179">Choi et al 2015</a>, <a class="bibr" href="#mpv17-mtdep.REF.bitting.2016.463" rid="mpv17-mtdep.REF.bitting.2016.463">Bitting & Hanson 2016</a>, <a class="bibr" href="#mpv17-mtdep.REF.kim.2016.74" rid="mpv17-mtdep.REF.kim.2016.74">Kim et al 2016</a>, <a class="bibr" href="#mpv17-mtdep.REF.mckiernan.2016.592" rid="mpv17-mtdep.REF.mckiernan.2016.592">McKiernan et al 2016</a>, <a class="bibr" href="#mpv17-mtdep.REF.elhattab.2018.461" rid="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab et al 2018</a>].</p><p>The vast majority of affected individuals (96/100) presented with an early-onset encephalohepatopathic (hepatocerebral) disease affecting mainly the nervous system and liver; mtDNA depletion is typically identified, particularly in liver. A later-onset neuromyopathic disease characterized by myopathy and neuropathy and associated with multiple mtDNA deletions in muscles has also rarely been described (4/100 affected individuals) [<a class="bibr" href="#mpv17-mtdep.REF.elhattab.2018.461" rid="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab et al 2018</a>].</p><p><b><i>MPV17</i>-related mtDNA maintenance defect, encephalohepatopathy form</b> is typically an early-onset disease that presents during the neonatal period (36 out of 96; 38%) or infancy (56 out of 96; 58%). Childhood onset (2-18 years) has been reported on rare occasions (4 out of 96; 4%) [<a class="bibr" href="#mpv17-mtdep.REF.elhattab.2018.461" rid="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab et al 2018</a>].</p><p>Clinical manifestations include hepatic and neurologic findings summarized in <a href="/books/NBK92947/table/mpv17-mtdep.T.clinical_manifestations_of/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTclinicalmanifestationsof">Table 2</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmpv17mtdepTclinicalmanifestationsof"><a href="/books/NBK92947/table/mpv17-mtdep.T.clinical_manifestations_of/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobmpv17mtdepTclinicalmanifestationsof"><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="mpv17-mtdep.T.clinical_manifestations_of"><a href="/books/NBK92947/table/mpv17-mtdep.T.clinical_manifestations_of/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTclinicalmanifestationsof">Table 2. </a></h4><p class="float-caption no_bottom_margin">Clinical Manifestations of <i>MPV17</i>-Related Encephalohepatopathy </p></div></div><p><b>Prognosis.</b>
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<i>MPV17</i>-related encephalohepatopathy typically has a poor prognosis due to early liver failure. Liver transplantation has been performed in some affected individuals, with high rates of post-transplantation death.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmpv17mtdepToutcomeofchildrenwithm"><a href="/books/NBK92947/table/mpv17-mtdep.T.outcome_of_children_with_m/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobmpv17mtdepToutcomeofchildrenwithm"><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="mpv17-mtdep.T.outcome_of_children_with_m"><a href="/books/NBK92947/table/mpv17-mtdep.T.outcome_of_children_with_m/?report=objectonly" target="object" rid-ob="figobmpv17mtdepToutcomeofchildrenwithm">Table 3. </a></h4><p class="float-caption no_bottom_margin">Outcome of Children with <i>MPV17</i>-Related Encephalohepatopathy </p></div></div><p><b><i>MPV17</i>-related mtDNA maintenance defect, neuromyopathy form</b> is a rare emerging phenotype described in four out of 100 (4%) affected individuals. Onset of symptoms is typically later and characterized by myopathy and neuropathy.</p><ul><li class="half_rhythm"><div>One individual presented during childhood, two during adolescence, and one during adulthood.</div></li><li class="half_rhythm"><div>All four individuals had myopathy and peripheral neuropathy.</div></li><li class="half_rhythm"><div>Liver manifestations were absent in two individuals, while the other two had milder liver involvement but without liver failure.</div></li><li class="half_rhythm"><div>Development was normal in all affected individuals.</div></li><li class="half_rhythm"><div>One individual had ptosis and ophthalmoplegia.</div></li><li class="half_rhythm"><div>Mitochondrial DNA was assessed in muscle tissue in two individuals and showed normal mtDNA content with multiple mtDNA deletions [<a class="bibr" href="#mpv17-mtdep.REF.blakely.2012.587" rid="mpv17-mtdep.REF.blakely.2012.587">Blakely et al 2012</a>, <a class="bibr" href="#mpv17-mtdep.REF.garone.2012.1648" rid="mpv17-mtdep.REF.garone.2012.1648">Garone et al 2012</a>, <a class="bibr" href="#mpv17-mtdep.REF.choi.2015.179" rid="mpv17-mtdep.REF.choi.2015.179">Choi et al 2015</a>].</div></li></ul></div><div id="mpv17-mtdep.GenotypePhenotype_Correlatio"><h3>Genotype-Phenotype Correlations</h3><p>No clear genotype-phenotype correlation exists. However, a trend for longer survival can be observed in individuals with biallelic pathogenic missense variants compared to individuals with biallelic null (nonsense, frameshift, deletions, and splice site) variants or individuals compound heterozygous for missense and null variants. In particular, individuals homozygous for <a href="/books/NBK92947/table/mpv17-mtdep.T.mpv17_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmpv17pathogenicvariants">p.Arg50Gln</a>, <a href="/books/NBK92947/table/mpv17-mtdep.T.mpv17_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmpv17pathogenicvariants">p.Pro98Leu</a>, or <a href="/books/NBK92947/table/mpv17-mtdep.T.mpv17_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmpv17pathogenicvariants">p.Arg41Gln</a> may carry a relatively better prognosis [<a class="bibr" href="#mpv17-mtdep.REF.elhattab.2018.461" rid="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab et al 2018</a>].</p></div><div id="mpv17-mtdep.Nomenclature"><h3>Nomenclature</h3><p>Navajo neurohepatopathy (NNH) was originally described as a distinct condition among Navajo children in the southwestern United States, but it is now clear that NNH is part of the <i>MPV17</i>-related mtDNA maintenance defect spectrum, falling under the encephalohepatopathy phenotype.</p><p>Encephalohepatopathic <i>MPV17</i>-related mtDNA maintenance defect may also be referred to as infantile hepatocerebral mtDNA depletion syndrome.</p></div><div id="mpv17-mtdep.Prevalence"><h3>Prevalence</h3><p>The prevalence of <i>MPV17</i>-related mtDNA maintenance defect is unknown but likely to be very low; only 100 affected individuals have been reported to date.</p></div></div><div id="mpv17-mtdep.Genetically_Related_Allelic"><h2 id="_mpv17-mtdep_Genetically_Related_Allelic_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are associated with pathogenic variants in <i>MPV17.</i></p></div><div id="mpv17-mtdep.Differential_Diagnosis"><h2 id="_mpv17-mtdep_Differential_Diagnosis_">Differential Diagnosis</h2><p><b>Encephalohepatopathic form</b> of <i>MPV17</i>-related mtDNA maintenance defect needs to be differentiated from other mtDNA maintenance defects that present with encephalohepatopathy (summarized in <a href="/books/NBK92947/table/mpv17-mtdep.T.mitochondrial_dna_maintena/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmitochondrialdnamaintena">Table 4a</a>). (See <a href="/books/n/gene/mtdna-md-ov/?report=reader">Mitochondrial DNA Maintenance Defects Overview</a>.)</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmpv17mtdepTmitochondrialdnamaintena"><a href="/books/NBK92947/table/mpv17-mtdep.T.mitochondrial_dna_maintena/?report=objectonly" target="object" title="Table 4a. " class="img_link icnblk_img" rid-ob="figobmpv17mtdepTmitochondrialdnamaintena"><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="mpv17-mtdep.T.mitochondrial_dna_maintena"><a href="/books/NBK92947/table/mpv17-mtdep.T.mitochondrial_dna_maintena/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmitochondrialdnamaintena">Table 4a. </a></h4><p class="float-caption no_bottom_margin">Mitochondrial DNA Maintenance Defects Presenting with Encephalohepatopathy </p></div></div><p>In addition, pathogenic variants in <i>BCS1L</i> (encoding a mitochondrial protein involved in complex III assembly) and <i>SCO1</i> (encoding a mitochondrial protein involved in complex IV assembly) have been associated with encephalopathy and hepatic dysfunction (OMIM <a href="https://omim.org/entry/124000" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">124000</a>, <a href="https://omim.org/entry/220110" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">220110</a>).</p><p>Infantile liver failure is also a feature of the disorders caused by pathogenic variants in <i>TRMU</i> (encoding mitochondria tRNA-specific 2-thiouridylase 1) and <i>GFM1</i> (encoding mitochondrial elongation factor G); mtDNA depletion is not a feature in these disorders (see <a href="/books/n/gene/trmu-def/?report=reader">TRMU Deficiency</a> and OMIM <a href="https://omim.org/entry/609060" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">609060</a>).</p><p><b>Neuromyopathic form</b> of <i>MPV17</i>-related mtDNA maintenance defect needs to be differentiated from other mtDNA maintenance defects that present with myopathy (summarized in <a href="/books/NBK92947/table/mpv17-mtdep.T.mitochondrial_dna_maintena_1/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmitochondrialdnamaintena1">Table 4b</a>). (See <a href="/books/n/gene/mtdna-md-ov/?report=reader">Mitochondrial DNA Maintenance Defects Overview</a>.)</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmpv17mtdepTmitochondrialdnamaintena1"><a href="/books/NBK92947/table/mpv17-mtdep.T.mitochondrial_dna_maintena_1/?report=objectonly" target="object" title="Table 4b. " class="img_link icnblk_img" rid-ob="figobmpv17mtdepTmitochondrialdnamaintena1"><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="mpv17-mtdep.T.mitochondrial_dna_maintena_1"><a href="/books/NBK92947/table/mpv17-mtdep.T.mitochondrial_dna_maintena_1/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmitochondrialdnamaintena1">Table 4b. </a></h4><p class="float-caption no_bottom_margin">Mitochondrial DNA Maintenance Defects Presenting with Myopathy </p></div></div></div><div id="mpv17-mtdep.Management"><h2 id="_mpv17-mtdep_Management_">Management</h2><div id="mpv17-mtdep.Evaluations_Following_Initia"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>MPV17</i>-related mtDNA maintenance defect, the evaluations summarized in <a href="/books/NBK92947/table/mpv17-mtdep.T.recommended_evaluations_fo/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTrecommendedevaluationsfo">Table 5</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmpv17mtdepTrecommendedevaluationsfo"><a href="/books/NBK92947/table/mpv17-mtdep.T.recommended_evaluations_fo/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobmpv17mtdepTrecommendedevaluationsfo"><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="mpv17-mtdep.T.recommended_evaluations_fo"><a href="/books/NBK92947/table/mpv17-mtdep.T.recommended_evaluations_fo/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTrecommendedevaluationsfo">Table 5. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with <i>MPV17</i>-Related mtDNA Maintenance Defect </p></div></div></div><div id="mpv17-mtdep.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Management should involve a multidisciplinary team including specialists in hepatology, neurology, nutrition, clinical genetics, and child development.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmpv17mtdepTtreatmentofmanifestation"><a href="/books/NBK92947/table/mpv17-mtdep.T.treatment_of_manifestation/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobmpv17mtdepTtreatmentofmanifestation"><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="mpv17-mtdep.T.treatment_of_manifestation"><a href="/books/NBK92947/table/mpv17-mtdep.T.treatment_of_manifestation/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTtreatmentofmanifestation">Table 6. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with <i>MPV17</i>-Related mtDNA Maintenance Defect </p></div></div><div id="mpv17-mtdep.Developmental_Delay__Intelle"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the US, early intervention is a federally funded program available in all states.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed.</p><p>
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<b>Ages 5-21 years</b>
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</p><ul><li class="half_rhythm"><div>In the US, an IEP based on the individual's level of function should be developed by the local public school district. Affected children are permitted to remain in the public school district until age 21.</div></li><li class="half_rhythm"><div>Discussion about transition plans including financial, vocation/employment, and medical arrangements should begin at age 12 years. Developmental pediatricians can provide assistance with transition to adulthood.</div></li></ul><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life.</p><p>Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</p><p>In the US:</p><ul><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div><div id="mpv17-mtdep.Motor_Dysfunction"><h4>Motor Dysfunction</h4><p>
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<b>Gross motor dysfunction</b>
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</p><ul><li class="half_rhythm"><div>Physical therapy is recommended to maximize mobility.</div></li><li class="half_rhythm"><div>Consider use of durable medical equipment as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</div></li></ul><p><b>Fine motor dysfunction.</b> Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.</p><p><b>Oral motor dysfunction.</b> Assuming that the individual is safe to eat by mouth, feeding therapy, typically from an occupational or speech therapist, is recommended for affected individuals who have difficulty feeding as a result of poor oral motor control.</p><p><b>Communication issues.</b> Consider evaluation for alternative means of communication (e.g., <a href="https://www.asha.org/NJC/AAC/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">augmentative and alternative communication</a> [AAC]) for individuals who have expressive language difficulties.</p></div></div><div id="mpv17-mtdep.Prevention_of_Secondary_Comp"><h3>Prevention of Secondary Complications</h3><p>Nutritional deficiencies (e.g., of fat-soluble vitamins) can be prevented by ensuring adequate intake and frequent assessment by a dietitian experienced in managing children with liver disease.</p></div><div id="mpv17-mtdep.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 severity of the condition:</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmpv17mtdepTrecommendedsurveillancef"><a href="/books/NBK92947/table/mpv17-mtdep.T.recommended_surveillance_f/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobmpv17mtdepTrecommendedsurveillancef"><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="mpv17-mtdep.T.recommended_surveillance_f"><a href="/books/NBK92947/table/mpv17-mtdep.T.recommended_surveillance_f/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTrecommendedsurveillancef">Table 7. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with <i>MPV17</i>-Related mtDNA Maintenance Defect </p></div></div></div><div id="mpv17-mtdep.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Prolonged fasting can lead to hypoglycemia and should be avoided.</p></div><div id="mpv17-mtdep.Evaluation_of_Relatives_at_R"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#mpv17-mtdep.Related_Genetic_Counseling_I">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="mpv17-mtdep.Therapies_Under_Investigatio"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="mpv17-mtdep.Genetic_Counseling"><h2 id="_mpv17-mtdep_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="mpv17-mtdep.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>MPV17</i>-related mtDNA maintenance defect is inherited in an autosomal recessive manner.</p></div><div id="mpv17-mtdep.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>MPV17</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> To date, individuals with <i>MPV17</i>-related mtDNA maintenance defect are not known to reproduce.</p><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of an <i>MPV17</i> pathogenic variant.</p></div><div id="mpv17-mtdep.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>MPV17</i> pathogenic variants in the family.</p></div><div id="mpv17-mtdep.Related_Genetic_Counseling_I"><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></div><div id="mpv17-mtdep.Prenatal_Testing_and_Preimpl"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>MPV17</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><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="mpv17-mtdep.Resources"><h2 id="_mpv17-mtdep_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>American Liver Foundation</b>
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</div><div><b>Phone:</b> 800-465-4837 (HelpLine)</div><div>
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<a href="http://www.liverfoundation.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">liverfoundation.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Canadian Liver Foundation</b>
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</div><div>Canada</div><div><b>Phone:</b> 800-563-5483</div><div><b>Email:</b> clf@liver.ca</div><div>
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<a href="http://www.liver.ca" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.liver.ca</a>
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</div></li><li class="half_rhythm"><div>
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<b>Childhood Liver Disease Research Network (ChiLDReN)</b>
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</div><div><b>Phone:</b> 720-777-2598</div><div><b>Email:</b> joan.hines@childrenscolorado.org</div><div>
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<a href="https://childrennetwork.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.childrennetwork.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Children's Liver Disease Foundation</b>
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</div><div>United Kingdom</div><div><b>Phone:</b> +44 (0) 121 212 3839</div><div><b>Email:</b> info@childliverdisease.org</div><div>
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<a href="http://www.childliverdisease.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">childliverdisease.org</a>
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</div></li><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="mpv17-mtdep.Molecular_Genetics"><h2 id="_mpv17-mtdep_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="figmpv17mtdepmolgenTA"><a href="/books/NBK92947/table/mpv17-mtdep.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobmpv17mtdepmolgenTA"><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="mpv17-mtdep.molgen.TA"><a href="/books/NBK92947/table/mpv17-mtdep.molgen.TA/?report=objectonly" target="object" rid-ob="figobmpv17mtdepmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">MPV17-Related Hepatocerebral Mitochondrial DNA Maintenance Defect: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmpv17mtdepmolgenTB"><a href="/books/NBK92947/table/mpv17-mtdep.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobmpv17mtdepmolgenTB"><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="mpv17-mtdep.molgen.TB"><a href="/books/NBK92947/table/mpv17-mtdep.molgen.TB/?report=objectonly" target="object" rid-ob="figobmpv17mtdepmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for MPV17-Related Hepatocerebral Mitochondrial DNA Maintenance Defect (View All in OMIM) </p></div></div><p><b>Gene structure.</b>
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<i>MPV17</i> spans 13.6 kb and comprises eight exons. For a detailed summary of gene and protein information, see <a href="/books/NBK92947/?report=reader#mpv17-mtdep.molgen.TA">Table A</a>.</p><p><b>Pathogenic variants.</b> To date, 48 <i>MPV17</i> pathogenic variants have been reported in children with <i>MPV17</i>-related mtDNA maintenance defect (<a href="/books/NBK92947/?report=reader#mpv17-mtdep.molgen.TA">Table A</a>; <a href="/books/NBK92947/table/mpv17-mtdep.T.mpv17_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmpv17pathogenicvariants">Table 8</a>). About half of those variants are missense and the remaining half includes nonsense, frameshift, and splice site variants, in-frame deletions, and large exon/multiexon deletions (summarized in <a class="bibr" href="#mpv17-mtdep.REF.elhattab.2018.461" rid="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab et al [2018]</a>). The majority of the <i>MPV17</i> pathogenic variants occur in one or a few families. However, homozygous c.149G>A has been reported in several affected individuals of Navajo ancestry. In addition, homozygous c.278A>C has been found in multiple families of Arab ancestry. Homozygosity and compound heterozygosity for c.293C>T have been described in several affected individuals of various ethnicities [<a class="bibr" href="#mpv17-mtdep.REF.elhattab.2018.461" rid="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab et al 2018</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmpv17mtdepTmpv17pathogenicvariants"><a href="/books/NBK92947/table/mpv17-mtdep.T.mpv17_pathogenic_variants/?report=objectonly" target="object" title="Table 8. " class="img_link icnblk_img" rid-ob="figobmpv17mtdepTmpv17pathogenicvariants"><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="mpv17-mtdep.T.mpv17_pathogenic_variants"><a href="/books/NBK92947/table/mpv17-mtdep.T.mpv17_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmpv17pathogenicvariants">Table 8. </a></h4><p class="float-caption no_bottom_margin"><i>MPV17</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b> The MPV17 protein is composed of 176 amino acids and is localized in the inner mitochondrial membrane [<a class="bibr" href="#mpv17-mtdep.REF.spinazzola.2006.570" rid="mpv17-mtdep.REF.spinazzola.2006.570">Spinazzola et al 2006</a>]. Molecular modeling of MPV17 predicted that the protein contains four transmembrane (TM) hydrophobic regions (TM1 from amino acids 18-38, TM2 53-73, TM3 94-114, and TM4 131-151) with five hydrophilic regions including three short linker regions connecting the TM spans and C-terminus and N- terminus at the same side of the membrane. Although C- and N-termini are located on the same side, it is unknown whether these termini are facing the matrix side or the intermembrane space side [<a class="bibr" href="#mpv17-mtdep.REF.wong.2007.1218" rid="mpv17-mtdep.REF.wong.2007.1218">Wong et al 2007</a>].</p><p>Recently, it was reported that MPV17 loss caused mitochondrial deoxynucleotide insufficiency [<a class="bibr" href="#mpv17-mtdep.REF.dalla_rosa.2016.e1005779" rid="mpv17-mtdep.REF.dalla_rosa.2016.e1005779">Dalla Rosa et al 2016</a>]. This finding, along with the localization of MPV17 in the inner mitochondrial membrane and animal models and cellular studies showing that Mpv17 forms a channel allowing small molecules to pass [<a class="bibr" href="#mpv17-mtdep.REF.l_llgen.2015.13" rid="mpv17-mtdep.REF.l_llgen.2015.13">Löllgen & Weiher 2015</a>], provide strong evidence that MPV17 functions as an inner mitochondrial membrane channel importing cytosolic nucleotides into the mitochondrion [<a class="bibr" href="#mpv17-mtdep.REF.elhattab.2018.461" rid="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab et al 2018</a>].</p><p><b>Abnormal gene product.</b>
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<i>MPV17</i> pathogenic variants result in dysfunctional MPV17 protein causing mitochondrial deoxynucleotide insufficiency and impaired mtDNA maintenance, leading to mtDNA depletion. Decrease in mtDNA content leads to insufficient production of respiratory chain components, resulting in impaired energy production and organ dysfunction [<a class="bibr" href="#mpv17-mtdep.REF.spinazzola.2006.570" rid="mpv17-mtdep.REF.spinazzola.2006.570">Spinazzola et al 2006</a>].</p></div><div id="mpv17-mtdep.Chapter_Notes"><h2 id="_mpv17-mtdep_Chapter_Notes_">Chapter Notes</h2><div id="mpv17-mtdep.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>17 May 2018 (ma) Comprehensive update posted live</div></li><li class="half_rhythm"><div>17 May 2012 (me) Review posted live</div></li><li class="half_rhythm"><div>27 February 2012 (aeh) Original submission</div></li></ul></div></div><div id="mpv17-mtdep.References"><h2 id="_mpv17-mtdep_References_">References</h2><div id="mpv17-mtdep.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.alhussaini.2014">Al-Hussaini A, Faqeih E, El-Hattab AW, Alfadhel M, Asery A, Alsaleem B, Bakhsh E, Ali A, Alasmari A, Lone K, Nahari A, Eyaid W, Al Balwi M, Craig K, Butterworth A, He L, Taylor RW. Clinical and molecular characteristics of mitochondrial DNA depletion syndrome associated with neonatal cholestasis and liver failure. J Pediatr. 2014;164:553-9.e1–2. [<a href="https://pubmed.ncbi.nlm.nih.gov/24321534" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24321534</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.aljasmi.2011.529">Al-Jasmi F, Penefsky HS, Souid A-K. The phosphorescence oxygen analyzer as a screening tool for disorders with impaired lymphocyte bioenergetics. <span><span class="ref-journal">Mol Genet Metab. </span>2011;<span class="ref-vol">104</span>:529–36.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21996136" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21996136</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.alsaman.2012.285">AlSaman A, Tomoum H, Invernizzi F, Zeviani M. Hepatocerebral form of mitochondrial DNA depletion syndrome due to mutation in MPV17 gene. <span><span class="ref-journal">Saudi J Gastroenterol. </span>2012;<span class="ref-vol">18</span>:285–9.</span> [<a href="/pmc/articles/PMC3409892/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3409892</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22824774" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22824774</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.bijarniamahay.2014.666">Bijarnia-Mahay S, Mohan N, Goyal D, Verma IC. Mitochondrial DNA depletion syndrome causing liver failure. <span><span class="ref-journal">Indian Pediatr. </span>2014;<span class="ref-vol">51</span>:666–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25129007" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25129007</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.bitting.2016.463">Bitting CP, Hanson JA. Navajo neurohepatopathy: a case report and literature review emphasizing clinicopathologic diagnosis. <span><span class="ref-journal">Acta Gastroenterol Belg. </span>2016;<span class="ref-vol">79</span>:463–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28209105" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28209105</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.blakely.2012.587">Blakely EL, Butterworth A, Hadden RDM, Bodi I, He L, McFarland R, Taylor RW. MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle. <span><span class="ref-journal">Neuromuscul Disord. </span>2012;<span class="ref-vol">22</span>:587–91.</span> [<a href="/pmc/articles/PMC3387382/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3387382</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22508010" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22508010</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.choi.2015.179">Choi Y-R, Hong YB, Jung S-C, Lee JH, Kim YJ, Park HJ, Lee J, Koo H, Lee J-S, Jwa DH, Jung N, Woo S-Y, Kim S-B, Chung KW, Choi B-O. A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy. <span><span class="ref-journal">BMC Neurol. </span>2015;<span class="ref-vol">15</span>:179.</span> [<a href="/pmc/articles/PMC4595119/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4595119</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26437932" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26437932</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.dalla_rosa.2016.e1005779">Dalla Rosa I, Cámara Y, Durigon R, Moss CF, Vidoni S, Akman G, Hunt L, Johnson MA, Grocott S, Wang L, Thorburn DR, Hirano M, Poulton J, Taylor RW, Elgar G, Martí R, Voshol P, Holt IJ, Spinazzola A. MPV17 loss causes deoxynucleotide insufficiency and slow DNA replication in mitochondria. <span><span class="ref-journal">PLoS Genet. </span>2016;<span class="ref-vol">12</span>:e1005779. </span> [<a href="/pmc/articles/PMC4711891/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4711891</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26760297" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26760297</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.elhattab.2010.300">El-Hattab AW, Li F-Y, Schmitt E, Zhang S, Craigen WJ, Wong L-JC. MPV17-associated hepatocerebral mitochondrial DNA depletion syndrome: new patients and novel mutations. <span><span class="ref-journal">Mol Genet Metab. </span>2010;<span class="ref-vol">99</span>:300–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20074988" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20074988</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab AW, Wang J, Dai H, Almannai M, Staufner C, Alfadhel M, Gambello MJ, Prasun P, Raza S, Lyons HJ, Afqi M, Saleh MAM, Faqeih EA, Alzaidan HI, Alshenqiti A, Flore LA, Hertecant J, Sacharow S, Barbouth DS, Murayama K, Shah AA, Lin HC, Wong LC. MPV17-related mitochondrial DNA maintenance defect: new cases and review of clinical, biochemical, and molecular aspects. <span><span class="ref-journal">Hum Mutat. </span>2018;<span class="ref-vol">39</span>:461–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29282788" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29282788</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.garone.2012.1648">Garone C, Rubio JC, Calvo SE, Naini A, Tanji K, Dimauro S, Mootha VK, Hirano M. MPV17 mutations causing adult-onset multisystemic disorder with multiple mitochondrial DNA deletions. <span><span class="ref-journal">Arch Neurol. </span>2012;<span class="ref-vol">69</span>:1648–51.</span> [<a href="/pmc/articles/PMC3894685/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3894685</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22964873" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22964873</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.kaji.2009.292">Kaji S, Murayama K, Nagata I, Nagasaka H, Takayanagi M, Ohtake A, Iwasa H, Nishiyama M, Okazaki Y, Harashima H, Eitoku T, Yamamoto M, Matsushita H, Kitamoto K, Sakata S, Katayama T, Sugimoto S, Fujimoto Y, Murakami J, Kanzaki S, Shiraki K. Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II. <span><span class="ref-journal">Mol Genet Metab. </span>2009;<span class="ref-vol">97</span>:292–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19520594" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19520594</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.karadimas.2006.544">Karadimas CL, Vu TH, Holve SA, Chronopoulou P, Quinzii C, Johnsen SD, Kurth J, Eggers E, Palenzuela L, Tanji K, Bonilla E, De Vivo DC, DiMauro S, Hirano M. Navajo neurohepatopathy is caused by a mutation in the MPV17 gene. <span><span class="ref-journal">Am J Hum Genet. </span>2006;<span class="ref-vol">79</span>:544–8.</span> [<a href="/pmc/articles/PMC1559552/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1559552</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16909392" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16909392</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.kim.2016.74">Kim J, Kang E, Kim Y, Kim J-M, Lee BH, Murayama K, Kim G-H, Choi IH, Kim KM, Yoo H-W. MPV17 mutations in patients with hepatocerebral mitochondrial DNA depletion syndrome. <span><span class="ref-journal">Mol Genet Metab Rep. </span>2016;<span class="ref-vol">8</span>:74–6.</span> [<a href="/pmc/articles/PMC4976613/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4976613</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27536553" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27536553</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.l_llgen.2015.13">Löllgen S, Weiher H. The role of the Mpv17 protein mutations of which cause mitochondrial DNA depletion syndrome (MDDS): lessons from homologs in different species. <span><span class="ref-journal">Biol Chem. </span>2015;<span class="ref-vol">396</span>:13–25.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25205723" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25205723</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.mckiernan.2016.592">McKiernan P, Ball S, Santra S, Foster K, Fratter C, Poulton J, Craig K, McFarland R, Rahman S, Hargreaves I, Gupte G, Sharif K, Taylor RW. Incidence of primary mitochondrial disease in children younger than 2 years presenting with acute liver failure. <span><span class="ref-journal">J Pediatr Gastroenterol Nutr. </span>2016;<span class="ref-vol">63</span>:592–7.</span> [<a href="/pmc/articles/PMC5113754/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5113754</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27482763" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27482763</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.mendelsohn.2014.37">Mendelsohn BA, Mehta N, Hameed B, Pekmezci M, Packman S, Ralph J. Adult-onset fatal neurohepatopathy in a woman caused by MPV17 mutation. <span><span class="ref-journal">JIMD Rep. </span>2014;<span class="ref-vol">13</span>:37–41.</span> [<a href="/pmc/articles/PMC4110326/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4110326</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24190800" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24190800</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.merkle.2012.e34">Merkle AN, Nascene DR, McKinney AM. MR imaging findings in the reticular formation in siblings with MPV17-related mitochondrial depletion syndrome. <span><span class="ref-journal">AJNR Am J Neuroradiol. </span>2012;<span class="ref-vol">33</span>:E34–5.</span> [<a href="/pmc/articles/PMC7966431/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7966431</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21511859" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21511859</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.navarrosastre.2008.234">Navarro-Sastre A, Martín-Hernández E, Campos Y, Quintana E, Medina E, de Las Heras RS, Lluch M, Muñoz A, del Hoyo P, Martín R, Gort L, Briones P, Ribes A. Lethal hepatopathy and leukodystrophy caused by a novel mutation in MPV17 gene: description of an alternative MPV17 spliced form. <span><span class="ref-journal">Mol Genet Metab. </span>2008;<span class="ref-vol">94</span>:234–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18329934" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18329934</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.nogueira.2012.764">Nogueira C, de Souza CFM, Husny A, Derks TGJ, Santorelli FM, Vilarinho L. MPV17: fatal hepatocerebral presentation in a Brazilian infant. <span><span class="ref-journal">Mol Genet Metab. </span>2012;<span class="ref-vol">107</span>:764.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23137571" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23137571</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.parini.2009.215">Parini R, Furlan F, Notarangelo L, Spinazzola A, Uziel G, Strisciuglio P, Concolino D, Corbetta C, Nebbia G, Menni F, Rossi G, Maggioni M, Zeviani M. Glucose metabolism and diet-based prevention of liver dysfunction in MPV17 mutant patients. <span><span class="ref-journal">J Hepatol. </span>2009;<span class="ref-vol">50</span>:215–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19012992" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19012992</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.piekutowskaabramczuk.2014.573">Piekutowska-Abramczuk D, Pronicki M, Strawa K, Karkucińska-Więckowska A, Szymańska-Dębińska T, Fidziańska A, Więckowski MR, Jurkiewicz D, Ciara E, Jankowska I, Sykut-Cegielska J, Krajewska-Walasek M, Płoski R, Pronicka E. Novel c.191C>G (p.Pro64Arg) MPV17 mutation identified in two pairs of unrelated Polish siblings with mitochondrial hepatoencephalopathy. <span><span class="ref-journal">Clin Genet. </span>2014;<span class="ref-vol">85</span>:573–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23829229" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23829229</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.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="mpv17-mtdep.REF.sarkhy.2014.175">Sarkhy AA, Al-Sunaid A, Abdullah A, AlFadhel M, Eiyad W. A novel MPV17 gene mutation in a Saudi infant causing fatal progressive liver failure. <span><span class="ref-journal">Ann Saudi Med. </span>2014;<span class="ref-vol">34</span>:175–8.</span> [<a href="/pmc/articles/PMC6074855/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6074855</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24894789" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24894789</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.spinazzola.2008.1108">Spinazzola A, Santer R, Akman OH, Tsiakas K, Schaefer H, Ding X, Karadimas CL, Shanske S, Ganesh J, Di Mauro S, Zeviani M. Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations. <span><span class="ref-journal">Arch Neurol. </span>2008;<span class="ref-vol">65</span>:1108–13.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18695062" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18695062</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.spinazzola.2006.570">Spinazzola A, Viscomi C, Fernandez-Vizarra E, Carrara F, D'Adamo P, Calvo S, Marsano RM, Donnini C, Weiher H, Strisciuglio P, Parini R, Sarzi E, Chan A, DiMauro S, Rötig A, Gasparini P, Ferrero I, Mootha VK, Tiranti V, Zeviani M. MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. <span><span class="ref-journal">Nat Genet. </span>2006;<span class="ref-vol">38</span>:570–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16582910" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16582910</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.uusimaa.2014.184">Uusimaa J, Evans J, Smith C, Butterworth A, Craig K, Ashley N, Liao C, Carver J, Diot A, Macleod L, Hargreaves I, Al-Hussaini A, Faqeih E, Asery A, Al Balwi M, Eyaid W, Al-Sunaid A, Kelly D, van Mourik I, Ball S, Jarvis J, Mulay A, Hadzic N, Samyn M, Baker A, Rahman S, Stewart H, Morris AA, Seller A, Fratter C, Taylor RW, Poulton J. Clinical, biochemical, cellular and molecular characterization of mitochondrial DNA depletion syndrome due to novel mutations in the MPV17 gene. <span><span class="ref-journal">Eur J Hum Genet. </span>2014;<span class="ref-vol">22</span>:184–91.</span> [<a href="/pmc/articles/PMC3895632/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3895632</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23714749" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23714749</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.vilarinho.2014.1056">Vilarinho S, Choi M, Jain D, Malhotra A, Kulkarni S, Pashankar D, Phatak U, Patel M, Bale A, Mane S, Lifton RP, Mistry PK. Individual exome analysis in diagnosis and management of paediatric liver failure of indeterminate aetiology. <span><span class="ref-journal">J Hepatol. </span>2014;<span class="ref-vol">61</span>:1056–63.</span> [<a href="/pmc/articles/PMC4203706/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4203706</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25016221" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25016221</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mpv17-mtdep.REF.wong.2007.1218">Wong L-JC, Brunetti-Pierri N, Zhang Q, Yazigi N, Bove KE, Dahms BB, Puchowicz MA, Gonzalez-Gomez I, Schmitt ES, Truong CK, Hoppel CL, Chou P-C, Wang J, Baldwin EE, Adams D, Leslie N, Boles RG, Kerr DS, Craigen WJ. Mutations in the MPV17 gene are responsible for rapidly progressive liver failure in infancy. <span><span class="ref-journal">Hepatology. </span>2007;<span class="ref-vol">46</span>:1218–27.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17694548" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17694548</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK92947_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">Julia Wang</span>, BS<div class="affiliation small">Program in Developmental Biology, Medical Scientist Training Program<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.mcb@gnaw.ailuj" class="oemail">ude.mcb@gnaw.ailuj</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Hongzheng Dai</span>, PhD<div class="affiliation small">Program in Developmental Biology, Medical Scientist Training Program<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.mcb@iad.gnehzgnoh" class="oemail">ude.mcb@iad.gnehzgnoh</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Mohammed Almannai</span>, MD, FAAP, FACMG<div class="affiliation small">Medical Genetics and Metabolic Consultant, Section of Medical Genetics<br />King Fahad Medical City<br />Riyadh, Saudi Arabia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="as.dem.cmfk@iannamlam" class="oemail">as.dem.cmfk@iannamlam</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><div class="contrib half_rhythm"><span itemprop="author">William J Craigen</span>, MD, PhD, FACMG<div class="affiliation small">Program in Developmental Biology, Medical Scientist Training Program<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.mcb@negiarcw" class="oemail">ude.mcb@negiarcw</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Lee-Jun C Wong</span>, PhD, FACMG<div class="affiliation small">Program in Developmental Biology, Medical Scientist Training Program<br />Baylor College of Medicine<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.mcb@gnowjl" class="oemail">ude.mcb@gnowjl</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">May 17, 2012</span>; Last Update: <span itemprop="dateModified">May 17, 2018</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, Wang J, Dai H, et al. MPV17-Related Mitochondrial DNA Maintenance Defect. 2012 May 17 [Updated 2018 May 17]. 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/mpph/?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/maps/?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="figobmpv17mtdepTd"><div id="mpv17-mtdep.Td" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92947/table/mpv17-mtdep.Td/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.Td_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mpv17-mtdep.Td_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>MPV17</i>-Related Mitochondrial DNA Maintenance Defect: Included Phenotypes <sup>1</sup></th></tr></thead><tbody><tr><td headers="hd_h_mpv17-mtdep.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div><i>MPV17</i>-related encephalohepatopathy, including Navajo neurohepatopathy <sup>2</sup></div></li><li class="half_rhythm"><div><i>MPV17</i>-related neuromyopathy</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="mpv17-mtdep.TF.d.1"><p class="no_margin">For other genetic causes of these phenotypes see <a href="#mpv17-mtdep.Differential_Diagnosis">Differential Diagnosis</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="mpv17-mtdep.TF.d.2"><p class="no_margin">See also <a href="#mpv17-mtdep.Nomenclature">Nomenclature</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmpv17mtdepTmoleculargenetictesting"><div id="mpv17-mtdep.T.molecular_genetic_testing" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>MPV17</i>-Related mtDNA Maintenance Defect</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92947/table/mpv17-mtdep.T.molecular_genetic_testing/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.T.molecular_genetic_testing_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mpv17-mtdep.T.molecular_genetic_testing_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_mpv17-mtdep.T.molecular_genetic_testing_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_mpv17-mtdep.T.molecular_genetic_testing_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_mpv17-mtdep.T.molecular_genetic_testing_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MPV17</i>
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</td><td headers="hd_h_mpv17-mtdep.T.molecular_genetic_testing_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_mpv17-mtdep.T.molecular_genetic_testing_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">94/98 (96%) <sup>4, 5</sup></td></tr><tr><td headers="hd_h_mpv17-mtdep.T.molecular_genetic_testing_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>6</sup></td><td headers="hd_h_mpv17-mtdep.T.molecular_genetic_testing_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4/98 (4%) <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="mpv17-mtdep.TF.1.1"><p class="no_margin">See <a href="/books/NBK92947/?report=reader#mpv17-mtdep.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="mpv17-mtdep.TF.1.2"><p class="no_margin">See <a href="#mpv17-mtdep.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="mpv17-mtdep.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="mpv17-mtdep.TF.1.4"><p class="no_margin">
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<a class="bibr" href="#mpv17-mtdep.REF.elhattab.2018.461" rid="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab et al [2018]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="mpv17-mtdep.TF.1.5"><p class="no_margin">Affected individuals of Navajo descent are commonly homozygotes for the <a href="/books/NBK92947/table/mpv17-mtdep.T.mpv17_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobmpv17mtdepTmpv17pathogenicvariants">p.Arg50Gln</a> pathogenic variant [<a class="bibr" href="#mpv17-mtdep.REF.karadimas.2006.544" rid="mpv17-mtdep.REF.karadimas.2006.544">Karadimas et al 2006</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="mpv17-mtdep.TF.1.6"><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="figobmpv17mtdepTclinicalmanifestationsof"><div id="mpv17-mtdep.T.clinical_manifestations_of" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Clinical Manifestations of <i>MPV17</i>-Related Encephalohepatopathy</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92947/table/mpv17-mtdep.T.clinical_manifestations_of/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.T.clinical_manifestations_of_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical Manifestations</th><th id="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="7" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hepatic</b>
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</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver dysfunction <sup>1</sup></td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">96/96 (100%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Liver failure <sup>2</sup></td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">87/96 (91%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Cholestasis</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">70/96 (73%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hepatomegaly</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">60/96 (63%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Steatosis</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">49/96 (51%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Liver cirrhosis</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20/96 (21%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hepatocellular cancer <sup>3</sup></td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3/96 (3%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1 hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" colspan="3" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="7" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic <sup>4</sup></b>
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</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental delay <sup>5</sup></td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">75/91 (82%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypotonia</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">67/91 (74%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Microcephaly</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">21/91 (23%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Peripheral neuropathy <sup>6</sup></td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">17/91 (19%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Seizures</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">9/91 (10%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Dystonia</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4/91 (4%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Ataxia</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3/91 (3%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1 hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" colspan="3" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Abnormalities</b>
|
|
<br />
|
|
<b>on brain MRI</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">White matter <sup>7</sup></td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">27/71 (38%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Brain stem signal</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6/71 (8%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Basal ganglia signal</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6/71 (8%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1 hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" colspan="3" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Gastrointestinal</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Failure to thrive <sup>8</sup></td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">82/91 (90%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gastrointestinal dysmotility <sup>9</sup></td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30/91 (33%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Feeding difficulties</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">28/91 (31%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1 hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" colspan="3" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Metabolic</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lactic acidosis <sup>10</sup></td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">72/91 (79%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypoglycemia <sup>11</sup></td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">55/91 (60%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1 hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" colspan="3" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="6" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Other</b>
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|
</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Renal tubulopathy</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">9/91 (10%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Nephrocalcinosis</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7/91 (8%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypoparathyroidism</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4/91 (4%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Retinopathy</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7/91 (8%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Nystagmus</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6/91 (7%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Corneal anesthesia & ulcers</td><td headers="hd_h_mpv17-mtdep.T.clinical_manifestations_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4/91 (4%)</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="mpv17-mtdep.TF.2.1"><p class="no_margin">Liver dysfunction typically presents as elevated transaminases, jaundice, hyperbilirubinemia, and coagulopathy.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="mpv17-mtdep.TF.2.2"><p class="no_margin">Liver disease progresses to liver failure typically during infancy and early childhood.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="mpv17-mtdep.TF.2.3"><p class="no_margin">Identified between ages seven and 11 years [<a class="bibr" href="#mpv17-mtdep.REF.karadimas.2006.544" rid="mpv17-mtdep.REF.karadimas.2006.544">Karadimas et al 2006</a>, <a class="bibr" href="#mpv17-mtdep.REF.elhattab.2010.300" rid="mpv17-mtdep.REF.elhattab.2010.300">El-Hattab et al 2010</a>, <a class="bibr" href="#mpv17-mtdep.REF.vilarinho.2014.1056" rid="mpv17-mtdep.REF.vilarinho.2014.1056">Vilarinho et al 2014</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="mpv17-mtdep.TF.2.4"><p class="no_margin">The neurologic manifestations can be overlooked or underestimated in children with early onset of severe hepatic involvement.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="mpv17-mtdep.TF.2.5"><p class="no_margin">Some affected individuals present with psychomotor delays during early infancy, while others have normal development early in life followed by loss of motor and cognitive abilities later in infancy or early childhood.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="mpv17-mtdep.TF.2.6"><p class="no_margin">Peripheral neuropathy typically manifests in early childhood with muscle weakness and wasting, decreased reflexes, and loss of sensation in the hands and feet.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="mpv17-mtdep.TF.2.7"><p class="no_margin">Diffuse white matter abnormalities may resemble leukodystrophy or hypomyelination.</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="mpv17-mtdep.TF.2.8"><p class="no_margin">Some children have normal growth, especially early in the course of the disease.</p></div></dd></dl><dl class="bkr_refwrap"><dt>9. </dt><dd><div id="mpv17-mtdep.TF.2.9"><p class="no_margin">May present as gastroesophageal reflux, recurrent vomiting, and/or diarrhea.</p></div></dd></dl><dl class="bkr_refwrap"><dt>10. </dt><dd><div id="mpv17-mtdep.TF.2.10"><p class="no_margin">Lactic acidosis is a biochemical finding with mild to moderate elevation of lactate (3-9 mmol/L).</p></div></dd></dl><dl class="bkr_refwrap"><dt>11. </dt><dd><div id="mpv17-mtdep.TF.2.11"><p class="no_margin">Hypoglycemia typically presents during the first six months of life and can be associated with lethargy, apnea, and/or seizures.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmpv17mtdepToutcomeofchildrenwithm"><div id="mpv17-mtdep.T.outcome_of_children_with_m" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Outcome of Children with <i>MPV17</i>-Related Encephalohepatopathy</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92947/table/mpv17-mtdep.T.outcome_of_children_with_m/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.T.outcome_of_children_with_m_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver Transplant?</th><th id="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Outcome</th><th id="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Yes (17/96; 18%)</b>
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</td><td headers="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Death <sup>1</sup></td><td headers="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10/17 (59%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Survival</td><td headers="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7/17 (41%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>No (79/96; 82%)</b>
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</td><td headers="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Death from liver failure <sup>2</sup></td><td headers="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">65/79 (82%)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Survival <sup>3</sup></td><td headers="hd_h_mpv17-mtdep.T.outcome_of_children_with_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">14/79 (18%)</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="mpv17-mtdep.TF.3.1"><p class="no_margin">Death most commonly occurred in the post-transplantation period due to sepsis, respiratory failure, or multiorgan failure.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="mpv17-mtdep.TF.3.2"><p class="no_margin">The majority died during infancy (52/65; 80%); some died during early childhood (1-5 years) (10/65; 15%), adolescence (2/65; 3%), or early adulthood (1/65; 2%).</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="mpv17-mtdep.TF.3.3"><p class="no_margin">The oldest reported affected individual is 25 years old [<a class="bibr" href="#mpv17-mtdep.REF.elhattab.2018.461" rid="mpv17-mtdep.REF.elhattab.2018.461">El-Hattab et al 2018</a>]. Note: This does NOT mean that survival past 25 years is not possible.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmpv17mtdepTmitochondrialdnamaintena"><div id="mpv17-mtdep.T.mitochondrial_dna_maintena" class="table"><h3><span class="label">Table 4a. </span></h3><div class="caption"><p>Mitochondrial DNA Maintenance Defects Presenting with Encephalohepatopathy</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92947/table/mpv17-mtdep.T.mitochondrial_dna_maintena/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.T.mitochondrial_dna_maintena_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder /<br />Phenotype</th><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">mtDNA Maintenance Defect</th><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Usual Age<br />of Onset</th><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common Clinical Manifestations</th></tr></thead><tbody><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MPV17</i>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Subject of this <i>GeneReview</i></td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Depletion</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal<br />period or<br />infancy</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Liver dysfunction/failure</div></li><li class="half_rhythm"><div>FTT</div></li><li class="half_rhythm"><div>Lactic acidosis</div></li></ul>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1" scope="row" 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_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/dguok-mtddepl/?report=reader">Deoxyguanosine kinase deficiency</a>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Depletion</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal<br />period</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Nystagmus</div></li><li class="half_rhythm"><div>Liver dysfunction/failure</div></li><li class="half_rhythm"><div>Lactic acidosis</div></li></ul>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>POLG</i>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/alpers/?report=reader">Alpers-Huttenlocher syndrome</a>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Depletion</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early<br />childhood</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Psychomotor regression</div></li><li class="half_rhythm"><div>Epilepsy</div></li><li class="half_rhythm"><div>Liver dysfunction/failure</div></li><li class="half_rhythm"><div>Hearing impairment</div></li></ul>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TFAM</i>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Encephalohepatopathy (OMIM <a href="https://omim.org/entry/617156" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617156</a>)</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Depletion</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal<br />period</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>IUGR</div></li><li class="half_rhythm"><div>Hypoglycemia</div></li><li class="half_rhythm"><div>Liver dysfunction/failure</div></li></ul>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TWNK</i>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Encephalohepatopathy (OMIM <a href="https://www.omim.org/entry/271245" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">271245</a>)</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Depletion</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal<br />period or<br />infancy</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Liver dysfunction/failure</div></li><li class="half_rhythm"><div>Lactic acidosis</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AR = autosomal recessive; DD = developmental delay; FTT = failure to thrive; IUGR = intrauterine growth restriction; MOI = mode of inheritance</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmpv17mtdepTmitochondrialdnamaintena1"><div id="mpv17-mtdep.T.mitochondrial_dna_maintena_1" class="table"><h3><span class="label">Table 4b. </span></h3><div class="caption"><p>Mitochondrial DNA Maintenance Defects Presenting with Myopathy</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92947/table/mpv17-mtdep.T.mitochondrial_dna_maintena_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.T.mitochondrial_dna_maintena_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">mtDNA<br />Maintenance Defect</th><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Usual Age<br />of Onset</th><th id="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common Clinical Manifestations<br />in Addition to Muscle Weakness</th></tr></thead><tbody><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>AGK</i>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sengers syndrome (OMIM <a href="https://www.omim.org/entry/212350" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">212350</a>)</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Depletion</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neonatal period</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>HCM</div></li><li class="half_rhythm"><div>Cataracts</div></li></ul>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_1" scope="row" 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_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/dguok-mtddepl/?report=reader">Deoxyguanosine kinase deficiency</a>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple<br />deletions</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early or mid-adulthood</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ptosis</div></li><li class="half_rhythm"><div>Ophthalmoplegia</div></li></ul>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DNA2</i>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Myopathy (OMIM <a href="https://omim.org/entry/615156" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">615156</a>)</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple deletions</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood or early adulthood</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ptosis</div></li><li class="half_rhythm"><div>Ophthalmoplegia</div></li></ul>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MGME1</i>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Myopathy (OMIM <a href="https://www.omim.org/entry/615084" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">615084</a>)</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Depletion & multiple deletions</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood or early adulthood</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ptosis</div></li><li class="half_rhythm"><div>Ophthalmoplegia</div></li></ul>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>POLG2</i>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Myopathy (See <a href="/books/n/gene/alpers/?report=reader"><i>POLG</i>-Related Disorders</a>.)</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple deletions</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy to adulthood</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ptosis</div></li><li class="half_rhythm"><div>Ophthalmoplegia</div></li></ul>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SLC25A4</i>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiomyopathy (OMIM <a href="https://omim.org/entry/615418" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">615418</a>)</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple deletions</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Exercise intolerance / easy fatigability</div></li><li class="half_rhythm"><div>HCM</div></li></ul>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Cardiomyopathy (OMIM <a href="https://www.omim.org/entry/617184" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617184</a>)</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Depletion</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Birth</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>HCM</div></li></ul>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_1" scope="row" 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_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/kss/?report=reader">Mitochondrial DNA depletion syndromes</a>
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</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Depletion</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy or childhood</td><td headers="hd_h_mpv17-mtdep.T.mitochondrial_dna_maintena_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Loss of acquired motor skills</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; HCM = hypertrophic cardiomyopathy; MOI = mode of inheritance</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmpv17mtdepTrecommendedevaluationsfo"><div id="mpv17-mtdep.T.recommended_evaluations_fo" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>MPV17</i>-Related mtDNA Maintenance Defect</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92947/table/mpv17-mtdep.T.recommended_evaluations_fo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.T.recommended_evaluations_fo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_1" rowspan="6" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gastrointestinal (liver)</b>
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</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver function tests</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver transaminases (ALT & AST), GGT, albumin, total & direct bilirubin, & coagulation profile (PT & PTT)</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Liver ultrasound</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess liver size, liver texture, & for presence of masses</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Alpha fetoprotein level</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To screen for hepatocellular carcinoma</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Hepatology / liver transplantation consultations</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Nutrition eval</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consultation w/gastroenterologist</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If dysmotility is suspected</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_1" rowspan="5" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic</b>
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|
</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/neurologist</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Developmental eval</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By developmental pediatrician</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Brain MRI</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To establish degree of CNS involvement; as a baseline for monitoring progression of neurologic disease</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Nerve conduction velocity</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To establish degree of peripheral nervous system involvement; as a baseline for monitoring progression of neurologic disease</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Electroencephalogram</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If seizures are suspected</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Metabolic</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Plasma glucose & lactate concentrations</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess lactic acidosis & hypoglycemia</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Renal</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Urinalysis & urine amino acids</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for renal tubulopathy</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Ocular</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic exam</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess corneal sensation & possible corneal ulcers/scarring</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Other</b>
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|
</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/clinical geneticist &/or genetic counselor</td><td headers="hd_h_mpv17-mtdep.T.recommended_evaluations_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></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">CNS = central nervous system</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmpv17mtdepTtreatmentofmanifestation"><div id="mpv17-mtdep.T.treatment_of_manifestation" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>MPV17</i>-Related mtDNA Maintenance Defect</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92947/table/mpv17-mtdep.T.treatment_of_manifestation/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.T.treatment_of_manifestation_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th></tr></thead><tbody><tr><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Liver failure</b>
|
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</td><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration of liver transplantation <sup>1</sup></td></tr><tr><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Hepatocellular carcinoma</b>
|
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</td><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Failure to thrive</b>
|
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</td><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Support from a dietitian experienced in managing children w/liver disease</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hypoglycemia</b>
|
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</td><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequent feeds & avoidance of fasting; uncooked cornstarch (1-2 g/kg/dose) <sup>2</sup></td></tr><tr><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Feeding difficulties</b>
|
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</td><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration of nasogastric or gastrostomy tube feeding</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gastrointestinal dysmotility</b>
|
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</td><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per gastroenterologist</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Seizures</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per neurologist</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Renal tubulopathy</b>
|
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</td><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per nephrologist</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Hypoparathyroidism</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per endocrinologist</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Corneal ulcers</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.treatment_of_manifestation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per ophthalmologist</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="mpv17-mtdep.TF.6.1"><p class="no_margin">Note: Liver transplantation is controversial (see <a href="#mpv17-mtdep.Clinical_Description">Clinical Description</a>).</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="mpv17-mtdep.TF.6.2"><p class="no_margin">Cornstarch may slow but not stop the progression of liver disease [<a class="bibr" href="#mpv17-mtdep.REF.spinazzola.2008.1108" rid="mpv17-mtdep.REF.spinazzola.2008.1108">Spinazzola et al 2008</a>, <a class="bibr" href="#mpv17-mtdep.REF.parini.2009.215" rid="mpv17-mtdep.REF.parini.2009.215">Parini et al 2009</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmpv17mtdepTrecommendedsurveillancef"><div id="mpv17-mtdep.T.recommended_surveillance_f" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>MPV17</i>-Related mtDNA Maintenance Defect</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92947/table/mpv17-mtdep.T.recommended_surveillance_f/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.T.recommended_surveillance_f_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Gastrointestinal</b>
|
|
<br />
|
|
<b>(liver)</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver function tests <sup>1</sup></td><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_3" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Depending on clinical severity</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Hepatic ultrasound</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Serum AFP level</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Nutritional assessment</td><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_3" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Neurologic</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic assessment</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Brain MRI, NCV, & EEG</td><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Based on clinical symptoms</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Metabolic</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Glucose level</td><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_3" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Depending on clinical severity</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Renal</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Urinalysis & urine amino acids to screen for renal tubulopathy</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Ocular</b>
|
|
</td><td headers="hd_h_mpv17-mtdep.T.recommended_surveillance_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmology eval</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">EEG = electroencephalogram; MRI = magnetic resonance imaging; NCV = nerve conduction velocity</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="mpv17-mtdep.TF.7.1"><p class="no_margin">Liver transaminases (ALT and AST), GGT, albumin, total and direct bilirubin, and coagulation profile (PT and PTT)</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmpv17mtdepmolgenTA"><div id="mpv17-mtdep.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>MPV17-Related Hepatocerebral Mitochondrial DNA Maintenance Defect: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92947/table/mpv17-mtdep.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_mpv17-mtdep.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_mpv17-mtdep.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_mpv17-mtdep.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_mpv17-mtdep.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_mpv17-mtdep.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_mpv17-mtdep.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_mpv17-mtdep.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="/gene/4358" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
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<i>MPV17</i>
|
|
</a>
|
|
</td><td headers="hd_b_mpv17-mtdep.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=4358" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">2p23<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_mpv17-mtdep.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/P39210" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Mitochondrial inner membrane protein Mpv17</a>
|
|
</td><td headers="hd_b_mpv17-mtdep.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/MPV17" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MPV17 database</a>
|
|
</td><td headers="hd_b_mpv17-mtdep.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=MPV17" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MPV17</a>
|
|
</td><td headers="hd_b_mpv17-mtdep.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=MPV17[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MPV17</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="mpv17-mtdep.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>;
|
|
chromosome locus from
|
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
|
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
|
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
|
<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmpv17mtdepmolgenTB"><div id="mpv17-mtdep.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for MPV17-Related Hepatocerebral Mitochondrial DNA Maintenance Defect (<a href="/omim/137960,256810" 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/NBK92947/table/mpv17-mtdep.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.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/137960" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">137960</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MITOCHONDRIAL INNER MEMBRANE PROTEIN MPV17; MPV17</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/256810" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">256810</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE); MTDPS6</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobmpv17mtdepTmpv17pathogenicvariants"><div id="mpv17-mtdep.T.mpv17_pathogenic_variants" class="table"><h3><span class="label">Table 8. </span></h3><div class="caption"><p><i>MPV17</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK92947/table/mpv17-mtdep.T.mpv17_pathogenic_variants/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mpv17-mtdep.T.mpv17_pathogenic_variants_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.122G>A</td><td headers="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg41Gln</td><td headers="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_3" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_002437.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_002437<wbr style="display:inline-block"></wbr>​.4</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_002428.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_002428<wbr style="display:inline-block"></wbr>​.1</a>
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</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.149G>A</td><td headers="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg50Gln</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.278A>C</td><td headers="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln93Pro</td></tr><tr><td headers="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.293C>T</td><td headers="hd_h_mpv17-mtdep.T.mpv17_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Pro98Leu</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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