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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>MECR-Related Neurologic Disorder - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
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<meta name="citation_title" content="MECR-Related Neurologic Disorder">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2019/05/09">
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<meta name="citation_author" content="Gali Heimer">
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<meta name="citation_author" content="Allison Gregory">
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<meta name="citation_author" content="Penelope Hogarth">
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<meta name="citation_author" content="Susan Hayflick">
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<meta name="citation_author" content="Bruria Ben Zeev">
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<meta name="citation_keywords" content="Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration (MEPAN)">
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<meta name="citation_keywords" content="Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration (MEPAN)">
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<meta name="citation_keywords" content="Enoyl-[acyl-carrier-protein] reductase, mitochondrial">
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<meta name="citation_keywords" content="MECR">
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<meta name="citation_keywords" content="MECR-Related Neurologic Disorder">
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<meta name="DC.Title" content="MECR-Related Neurologic Disorder">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Gali Heimer">
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<meta name="DC.Contributor" content="Allison Gregory">
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<meta name="DC.Contributor" content="Penelope Hogarth">
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<meta name="DC.Contributor" content="Susan Hayflick">
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<meta name="DC.Contributor" content="Bruria Ben Zeev">
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<meta name="DC.Date" content="2019/05/09">
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<meta name="description" content="MECR-related neurologic disorder is characterized by a progressive childhood-onset movement disorder and optic atrophy; intellect is often – but not always – preserved. The movement disorder typically presents between ages one and 6.5 years and is mainly dystonia that can be accompanied by chorea and/or ataxia. Over time some affected individuals require assistive devices for mobility. Speech fluency and intelligibility are progressively impaired due to dysarthria. Optic atrophy typically develops between ages four and 12 years and manifests as reduced visual acuity, which can include functional blindness (also known as legal blindness) in adulthood. Because only 13 affected individuals are known to the authors, and because nearly half of them were diagnosed retrospectively as adults, the natural history of disease progression and other aspects of the phenotype have not yet been completely defined.">
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<meta name="og:description" content="MECR-related neurologic disorder is characterized by a progressive childhood-onset movement disorder and optic atrophy; intellect is often – but not always – preserved. The movement disorder typically presents between ages one and 6.5 years and is mainly dystonia that can be accompanied by chorea and/or ataxia. Over time some affected individuals require assistive devices for mobility. Speech fluency and intelligibility are progressively impaired due to dysarthria. Optic atrophy typically develops between ages four and 12 years and manifests as reduced visual acuity, which can include functional blindness (also known as legal blindness) in adulthood. Because only 13 affected individuals are known to the authors, and because nearly half of them were diagnosed retrospectively as adults, the natural history of disease progression and other aspects of the phenotype have not yet been completely defined.">
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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="_NBK540959_"><span class="title" itemprop="name"><i>MECR</i>-Related Neurologic Disorder</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration (MEPAN)</div><p class="contribs">Heimer G, Gregory A, Hogarth P, et al.</p><p class="fm-aai"><a href="#_NBK540959_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 16 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="mecr-dis.Summary" itemprop="description"><h2 id="_mecr-dis_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>MECR</i>-related neurologic disorder is characterized by a progressive childhood-onset movement disorder and optic atrophy; intellect is often – but not always – preserved. The movement disorder typically presents between ages one and 6.5 years and is mainly dystonia that can be accompanied by chorea and/or ataxia. Over time some affected individuals require assistive devices for mobility. Speech fluency and intelligibility are progressively impaired due to dysarthria. Optic atrophy typically develops between ages four and 12 years and manifests as reduced visual acuity, which can include functional blindness (also known as legal blindness) in adulthood. Because only 13 affected individuals are known to the authors, and because nearly half of them were diagnosed retrospectively as adults, the natural history of disease progression and other aspects of the phenotype have not yet been completely defined.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>MECR</i>-related neurologic disorder is established in a proband with a childhood-onset movement disorder and biallelic (compound heterozygous or homozygous) pathogenic variants in <i>MECR</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Visual aids for decreased visual acuity due to optic atrophy; occupational therapy and physical therapy to maintain range of movement and special aids (e.g., braces, walkers, wheelchairs) to maintain/improve mobility; speech therapy for dysarthria and augmentative communication if needed. Medications that may relieve dystonia include anticholinergic agents, baclofen, and benzodiazepines.</p><p><i>Surveillance:</i> The following yearly examinations are warranted: ophthalmologic (need for additional visual aids), neurologic (need for medications to relieve dystonia), speech therapy (need for augmentative communication), cognitive evaluation, and feeding evaluation (assess risk of aspiration).</p><p><i>Agents/circumstances to avoid:</i> Stress and febrile illness as much as possible as these are presumed to exacerbate disease progression. Discuss anesthetic risks with a patient's medical team prior to surgical procedures.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>MECR</i>-related neurologic disorder is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the <i>MECR</i> pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic diagnosis are possible.</p></div></div><div id="mecr-dis.Diagnosis"><h2 id="_mecr-dis_Diagnosis_">Diagnosis</h2><p>To date no formal diagnostic criteria have been published for <i>MECR</i>-related neurologic disorder.</p><div id="mecr-dis.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>MECR</i>-related neurologic disorder <b>should be suspected</b> in individuals with the following clinical findings, neuroimaging findings, and ethnicity.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Childhood-onset dystonia, chorea, and other movement disorders: ages 1-6.5 years</div></li><li class="half_rhythm"><div>Childhood-onset optic atrophy: typically ages 4-12 years. Note that optic atrophy is not necessary to consider the diagnosis of <i>MECR</i>-related neurologic disorder in a young child as it may appear several years after the onset of the movement disorder.</div></li></ul><p><b>Neuroimaging findings.</b> On MRI, bilateral hyperintense T<sub>2</sub>-weighted signal in one or more structures of the basal ganglia (i.e., caudate, putamen, or pallidum) evident at time of onset of dystonia (<a class="figpopup" href="/books/NBK540959/figure/mecr-dis.F1/?report=objectonly" target="object" rid-figpopup="figmecrdisF1" rid-ob="figobmecrdisF1">Figure 1</a>)</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figmecrdisF1" co-legend-rid="figlgndmecrdisF1"><a href="/books/NBK540959/figure/mecr-dis.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figmecrdisF1" rid-ob="figobmecrdisF1"><img class="small-thumb" src="/books/NBK540959/bin/mecr-dis-Image001.gif" src-large="/books/NBK540959/bin/mecr-dis-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndmecrdisF1"><h4 id="mecr-dis.F1"><a href="/books/NBK540959/figure/mecr-dis.F1/?report=objectonly" target="object" rid-ob="figobmecrdisF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Magnetic resonance imaging of individuals with <i>MECR</i>-related neurologic disorder showing hyperintense T<sub>2</sub>-weighted and FLAIR signals within the basal ganglia A. T<sub>2</sub>-weighted axial section demonstrating hyperintense pallidal signal (arrow) (Family G, Patient <a href="/books/NBK540959/figure/mecr-dis.F1/?report=objectonly" target="object" rid-ob="figobmecrdisF1">(more...)</a></p></div></div><p><b>Ethnicity.</b> Ashkenazi Jewish heritage. Note that while <i>MECR</i>-related neurologic disorder is more frequent in Ashkenazi Jews, it also occurs in persons of other ethnicities.</p></div><div id="mecr-dis.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>MECR</i>-related neurologic disorder <b>is established</b> in a proband with <a href="#mecr-dis.Suggestive_Findings">Suggestive Findings</a> and biallelic (compound heterozygous or homozygous) pathogenic (or likely pathogenic) variants in <i>MECR</i> by molecular genetic testing (<a href="/books/NBK540959/table/mecr-dis.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobmecrdisTmoleculargenetictestinguse">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="#mecr-dis.REF.richards.2015.405" rid="mecr-dis.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>MECR</i> variants of uncertain significance (or of one known <i>MECR</i> pathogenic variant and one <i>MECR</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing or a multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of <i>MECR</i>-related neurologic disorder is distinctive, children with findings described in <a href="#mecr-dis.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#mecr-dis.Option_1">Option 1</a>), whereas those with a phenotype indistinguishable from other childhood-onset dystonias with bilateral symmetric basal ganglia signal intensity changes are more likely to be diagnosed using genomic testing (see <a href="#mecr-dis.Option_2">Option 2</a>).</p><div id="mecr-dis.Option_1"><h4>Option 1</h4><p>When the phenotypic and imaging findings suggest the diagnosis of <i>MECR</i>-related neurologic disorder, molecular genetic testing approaches can include <b>single-gene testing</b> or use of a <b>multigene panel</b>.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-gene testing.</b> Sequence analysis of <i>MECR</i> is performed first. If only one pathogenic variant is found, gene-targeted deletion/duplication analysis could be considered; however, to date no exon or whole-gene deletions have been reported.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A dystonia multigene panel</b> that includes <i>MECR</i> and other genes of interest (see <a href="#mecr-dis.Differential_Diagnosis">Differential Diagnosis</a>) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Of note, given the novelty and rarity of <i>MECR</i>-related neurologic disorder, many panels for dystonia may not yet include this gene. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul></div><div id="mecr-dis.Option_2"><h4>Option 2</h4><p>When the phenotype is indistinguishable from many other disorders of childhood-onset dystonia, <b>comprehensive</b>
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<b>genomic testing</b> (which does not require the clinician to determine which gene[s] are likely involved) is the best option. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</p><p>If exome sequencing is not diagnostic, <b>exome array</b> (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. Note: To date such variants have not been identified as a cause of <i>MECR</i>-related neurologic disorder.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmecrdisTmoleculargenetictestinguse"><a href="/books/NBK540959/table/mecr-dis.T.molecular_genetic_testing_use/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobmecrdisTmoleculargenetictestinguse"><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="mecr-dis.T.molecular_genetic_testing_use"><a href="/books/NBK540959/table/mecr-dis.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobmecrdisTmoleculargenetictestinguse">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>MECR</i>-Related Neurologic Disorder </p></div></div></div></div></div><div id="mecr-dis.Clinical_Characteristics"><h2 id="_mecr-dis_Clinical_Characteristics_">Clinical Characteristics</h2><div id="mecr-dis.Clinical_Description"><h3>Clinical Description</h3><p>To date, the authors know of 13 individuals with <i>MECR</i>-related neurologic disorder: seven (5 probands and 2 family members) described by <a class="bibr" href="#mecr-dis.REF.heimer.2016.1229" rid="mecr-dis.REF.heimer.2016.1229">Heimer et al [2016]</a>, and six ascertained more recently by the authors (1 individual and 2 sets of sibs). The common clinical phenotype in these 13 individuals is characterized by childhood-onset movement disorder followed by optic atrophy, and often – but not always – preserved intellect. Similar to other metabolic disorders, symptoms may fluctuate temporally with febrile illnesses. In one instance, the young child never fully regained motor skills lost after fever. Because of the limited number of affected individuals reported to date, and because nearly half of them were diagnosed retrospectively as adults, the natural history of progression of the known features of the disorder as well as other possible aspects of the phenotype have not yet been completely defined.</p><p>The motor disability and dysarthria progress with time. Severity may vary between affected individuals, even within the same family. <a class="bibr" href="#mecr-dis.REF.heimer.2016.1229" rid="mecr-dis.REF.heimer.2016.1229">Heimer et al [2016]</a> describe a male age 46 years (Family C, Patient II:2) with unintelligible speech and contractures who was confined to a wheelchair and totally dependent for all activities of daily living, whereas his brother age 28 years (Patient II:8) walked independently despite limb dystonia and had slightly slurred dysarthric – but intelligible – speech.</p><p>In a different family of two affected brothers (ages 5 and 6 years), one had progressive dystonia, spasticity, and ataxia whereas the other had predominantly hypotonia and neck muscle weakness; neither has walked independently [Family F; Author, unpublished observations].</p><p>In a third family with three affected sisters, the oldest (currently age 15 years) started walking at about age two years, then exhibited pronounced chorea from age 5.5 years and dystonia from age 12 years. The youngest (currently age 4 years) exhibited arm dystonia at age one year, walked independently at age 22 months, and currently manifests dystonia of all limbs and facial chorea. In contrast, the middle sister (currently age 5.5 years) started walking at age 12 months; neurologic examination revealed minimal dystonia of the left leg of which the parents had previously been unaware [Family G; Author, unpublished observations].</p><p><b>Neurologic manifestations.</b> The presenting manifestation is an involuntary movement disorder, mainly dystonia that can be accompanied by chorea and/or ataxia.</p><p>Onset of the movement disorder is during early childhood (12 months–6.5 years). However, a history of hypotonia, increased laxity, and delayed motor development from the first year of life is possible.</p><p>The motor disability gradually progresses; over time, some affected individuals require a walker or wheelchair for ambulation. Some with earlier onset and more rapid progression may never walk independently.</p><p>Speech fluency and intelligibility are progressively impaired due to dysarthria. In some cases (e.g., the three sisters in Family G) articulation may be impaired at onset of speech, whereas in other children (e.g., the two brothers in Family F) speech may never develop despite relative preservation of receptive language.</p><p>Cognition was unaffected or relatively spared in five of the seven reported by <a class="bibr" href="#mecr-dis.REF.heimer.2016.1229" rid="mecr-dis.REF.heimer.2016.1229">Heimer et al [2016]</a> (Family E). Of two brothers with impaired cognition, linguistic skills and executive function deteriorated to an extremely low range at age nine years in one (Patient II:1), whereas the other (Patient II:3) was reported to have low average verbal comprehension with extremely low function on the other WISC IV indices.</p><p>Although the oldest of the three sisters in Family G was suspected of having polyneuropathy (areflexia and decreased sensation noted around age two years), these findings were not evident on more recent examination. Furthermore, conflicting results of two nerve conduction velocity (NCV) tests several years apart cast doubt on whether these findings resulted from polyneuropathy or were other manifestations of <i>MECR</i>-related neurologic disorder.</p><p>To date, seizures and encephalopathy have not been reported.</p><p><b>Ocular manifestations.</b> Optic atrophy develops within seven years of the onset of dystonia (i.e., between ages 4 and 12 years). It manifests as reduced visual acuity, which can include functional blindness in adulthood in some individuals.</p><p>Abnormal eye movements (nystagmus or roving eye movements) can also be seen.</p><p><b>Life expectancy.</b> All currently known affected individuals are alive; two are in their fifth decade.</p><p><b>Laboratory tests.</b> No consistent biomarker was found. Of note, elevated urinary 3 OH-isovaleric acid was found in one individual and 3 methyl glutaconic acid in another.</p></div><div id="mecr-dis.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No clear genotype-phenotype correlations have been observed. Of the 13 currently known affected individuals, 12 are compound heterozygotes with various combinations of a missense variant and nonsense variant, and one is a homozygote for a missense variant [<a class="bibr" href="#mecr-dis.REF.heimer.2016.1229" rid="mecr-dis.REF.heimer.2016.1229">Heimer et al 2016</a> and personal communication]. These findings suggest that the combination of two nonsense variants could either be incompatible with life or give rise to a more severe phenotype.</p></div><div id="mecr-dis.Prevalence"><h3>Prevalence</h3><p>To the authors' knowledge, only 13 individuals from eight families have been diagnosed with <i>MECR</i>-related neurologic disorder to date. Five of the eight families were of Ashkenazi Jewish origin, suggesting possible increased prevalence in this population [<a class="bibr" href="#mecr-dis.REF.heimer.2016.1229" rid="mecr-dis.REF.heimer.2016.1229">Heimer et al 2016</a> and personal communication].</p><p>Unpublished results based on the <a href="https://ibd.broadinstitute.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Inflammatory Bowel Disease Exomes Browser</a> containing more than 5,500 exomes of Ashkenazi Jewish individuals revealed an increased frequency of two pathogenic variants among the Ashkenazi Jewish population:</p><ul><li class="half_rhythm"><div><a href="/books/NBK540959/table/mecr-dis.T.mecr_pathogenic_variants_disc/?report=objectonly" target="object" rid-ob="figobmecrdisTmecrpathogenicvariantsdisc">c.695G>A</a> missense variant in 18/5,598; variant frequency of 1:311</div></li><li class="half_rhythm"><div><a href="/books/NBK540959/table/mecr-dis.T.mecr_pathogenic_variants_disc/?report=objectonly" target="object" rid-ob="figobmecrdisTmecrpathogenicvariantsdisc">c.830+2dupT</a> splice site variant in 41/5,576; variant frequency of 1:136</div></li></ul></div></div><div id="mecr-dis.Genetically_Related_Allelic_Dis"><h2 id="_mecr-dis_Genetically_Related_Allelic_Dis_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with pathogenic variants in <i>MECR</i>.</p></div><div id="mecr-dis.Differential_Diagnosis"><h2 id="_mecr-dis_Differential_Diagnosis_">Differential Diagnosis</h2><p>The differential diagnosis of <i>MECR</i>-related neurologic disorder includes disorders that combine the clinical features of childhood-onset movement disorder (mainly dystonia [see <a href="/books/n/gene/dystonia-ov/?report=reader">Hereditary Dystonia Overview</a>] but also ataxia and chorea) and the MRI findings of signal abnormality in the basal ganglia present when the movement disorder appears.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmecrdisTdisorderswithdystoniaandm"><a href="/books/NBK540959/table/mecr-dis.T.disorders_with_dystonia_and_m/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobmecrdisTdisorderswithdystoniaandm"><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="mecr-dis.T.disorders_with_dystonia_and_m"><a href="/books/NBK540959/table/mecr-dis.T.disorders_with_dystonia_and_m/?report=objectonly" target="object" rid-ob="figobmecrdisTdisorderswithdystoniaandm">Table 2. </a></h4><p class="float-caption no_bottom_margin">Disorders with Dystonia and MRI Signal Abnormality in the Basal Ganglia to Consider in the Differential Diagnosis of <i>MECR</i>-Related Neurologic Disorder </p></div></div></div><div id="mecr-dis.Management"><h2 id="_mecr-dis_Management_">Management</h2><div id="mecr-dis.Evaluations_Following_Initial_D"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>MECR</i>-related neurologic disorder, the evaluations summarized in <a href="/books/NBK540959/table/mecr-dis.T.recommended_evaluations_follo/?report=objectonly" target="object" rid-ob="figobmecrdisTrecommendedevaluationsfollo">Table 3</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="figmecrdisTrecommendedevaluationsfollo"><a href="/books/NBK540959/table/mecr-dis.T.recommended_evaluations_follo/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobmecrdisTrecommendedevaluationsfollo"><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="mecr-dis.T.recommended_evaluations_follo"><a href="/books/NBK540959/table/mecr-dis.T.recommended_evaluations_follo/?report=objectonly" target="object" rid-ob="figobmecrdisTrecommendedevaluationsfollo">Table 3. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis </p></div></div></div><div id="mecr-dis.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>The following are appropriate:</p><ul><li class="half_rhythm"><div>Visual aids can be used in cases of decreased visual acuity due to optic atrophy.</div></li><li class="half_rhythm"><div>Physiotherapy can be used to maintain range of movement.</div></li><li class="half_rhythm"><div>Occupational therapy can be used as appropriate to develop and maintain skills related to activities of daily living, which will vary across the life span.</div></li><li class="half_rhythm"><div>Special aids such as braces, walkers, and wheelchairs can maintain/improve mobility.</div></li><li class="half_rhythm"><div>Speech therapy, if speech dysarthria is present, and assessment for augmentative communication devices</div></li><li class="half_rhythm"><div>Medications that may relieve dystonia, such as anticholinergic agents, baclofen, and benzodiazepines, can be considered.</div><ul><li class="half_rhythm"><div>Anticholinergic agents act peripherally on the neuromuscular junction, but can have a variety of adverse central nervous system (CNS) effects.</div></li><li class="half_rhythm"><div>Baclofen, which works on GABA<sub>B</sub> receptors and functions as a CNS depressant and skeletal muscle relaxant, can be administered either through an intrathecal pump or systemically (enterally).</div></li><li class="half_rhythm"><div>Benzodiazepines, which are GABA<sub>A</sub> agonists, can reduce muscle tone and alleviate the dystonia; however, they also cause sedation.</div></li></ul></li><li class="half_rhythm"><div>Deep brain stimulation (DBS): While some patients with severe dystonia are treated with DBS, experience with <i>MECR</i>-related neurologic disorder is limited. To date, there are no reports of individuals with this disorder treated with DBS. Moreover, due to the existence of basal ganglia lesions, DBS may not be suitable for many persons with <i>MECR</i>-related neurologic disorder.</div></li><li class="half_rhythm"><div>Of the three sisters (Family G; Author, unpublished observations), two are treated for ADHD: one with Vyvanse® (lisdexamfetamine dimesylate), which seems to also improve her dystonia and dysarthria; the other with Adderall, which seems to improve her dystonia and balance.</div></li></ul></div><div id="mecr-dis.Surveillance"><h3>Surveillance</h3><p>The following are recommended:</p><ul><li class="half_rhythm"><div>Yearly eye examination to determine need for additional visual aids</div></li><li class="half_rhythm"><div>Yearly neurologic assessment to determine need for additional interventions, including speech therapy</div></li></ul></div><div id="mecr-dis.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Disease progression is presumed to be exacerbated by stress or febrile illness; therefore, prevention of these – to the extent possible – is recommended.</p><p>One patient reported onset of significant new, long-term motor symptoms following extended anesthesia with propofol. As with other mitochondrial disorders, anesthetic considerations should be discussed with a patient's medical team prior to any surgical procedure [<a class="bibr" href="#mecr-dis.REF.niezgoda.2013.785" rid="mecr-dis.REF.niezgoda.2013.785">Niezgoda & Morgan 2013</a>].</p><p>In one of the sisters (Family G), a test dose of dopamine worsened her chorea significantly.</p></div><div id="mecr-dis.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#mecr-dis.Related_Genetic_Counseling_Issu">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="mecr-dis.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>The pathomechanism of <i>MECR</i>-related neurologic disorder suggests the possible therapeutic effect of supplementation with lipoic acid (LA) and octanoic acid (C8). One individual showed remarkable improvement after receiving LA and a nutritional supplement high in C8 within three months of symptom onset [<a class="bibr" href="#mecr-dis.REF.heimer.2016.1229" rid="mecr-dis.REF.heimer.2016.1229">Heimer et al 2016</a>]. The authors are currently offering their patients treatment with a Mito Cocktail of coenzyme Q10, riboflavin, thiamine, and alpha lipoic acid with the addition of octanoic acid, vitamin E, and vitamin C (see also <a href="#mecr-dis.Author_Notes">Author Notes</a>). Of note, the efficacy of this regimen for treatment of <i>MECR</i>-related neurologic disorder has yet to be proven in an evidence-based manner.</p><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="mecr-dis.Genetic_Counseling"><h2 id="_mecr-dis_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="mecr-dis.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>MECR</i>-related neurologic disorder is inherited in an autosomal recessive manner.</p></div><div id="mecr-dis.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>MECR</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> Unless an affected individual's reproductive partner also has <i>MECR</i>-related neurologic disorder or is a carrier, offspring will be obligate heterozygotes (carriers) for a pathogenic variant in <i>MECR</i>.</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>MECR</i> pathogenic variant.</p></div><div id="mecr-dis.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>MECR</i> pathogenic variants in the family.</p></div><div id="mecr-dis.Related_Genetic_Counseling_Issu"><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 affected, are carriers, or are at risk of being carriers.</div></li></ul></div><div id="mecr-dis.Prenatal_Testing_and_Preimplant"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>MECR</i> pathogenic variants have been identified in an affected family member, prenatal testing 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="mecr-dis.Resources"><h2 id="_mecr-dis_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>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></ul>
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</div><div id="mecr-dis.Molecular_Genetics"><h2 id="_mecr-dis_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="figmecrdismolgenTA"><a href="/books/NBK540959/table/mecr-dis.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobmecrdismolgenTA"><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="mecr-dis.molgen.TA"><a href="/books/NBK540959/table/mecr-dis.molgen.TA/?report=objectonly" target="object" rid-ob="figobmecrdismolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">MECR-Related Neurologic Disorder: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmecrdismolgenTB"><a href="/books/NBK540959/table/mecr-dis.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobmecrdismolgenTB"><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="mecr-dis.molgen.TB"><a href="/books/NBK540959/table/mecr-dis.molgen.TB/?report=objectonly" target="object" rid-ob="figobmecrdismolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for MECR-Related Neurologic Disorder (View All in OMIM) </p></div></div><p><b>Gene structure.</b>
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<i>MECR</i> (<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_016011.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_016011.4</a>) comprises ten exons and a total of 2,539 bp. Multiple transcript variants have been reported. (For a detailed summary of gene, transcript, and protein information, see <a href="/books/NBK540959/?report=reader#mecr-dis.molgen.TA">Table A</a>, <b>Gene</b>.)</p><p><b>Pathogenic variants.</b> To date, six pathogenic variants have been described: three missense, two nonsense, and one splice site [<a class="bibr" href="#mecr-dis.REF.heimer.2016.1229" rid="mecr-dis.REF.heimer.2016.1229">Heimer et al 2016</a>]; see <a href="/books/NBK540959/?report=reader#mecr-dis.molgen.TA">Table A</a>, <b>Databases</b>. The frequency of two pathogenic variants is increased in Ashkenazi Jewish populations (see <a href="#mecr-dis.Prevalence">Prevalence</a>; <a href="/books/NBK540959/table/mecr-dis.T.mecr_pathogenic_variants_disc/?report=objectonly" target="object" rid-ob="figobmecrdisTmecrpathogenicvariantsdisc">Table 4</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmecrdisTmecrpathogenicvariantsdisc"><a href="/books/NBK540959/table/mecr-dis.T.mecr_pathogenic_variants_disc/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobmecrdisTmecrpathogenicvariantsdisc"><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="mecr-dis.T.mecr_pathogenic_variants_disc"><a href="/books/NBK540959/table/mecr-dis.T.mecr_pathogenic_variants_disc/?report=objectonly" target="object" rid-ob="figobmecrdisTmecrpathogenicvariantsdisc">Table 4. </a></h4><p class="float-caption no_bottom_margin"><i>MECR</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b>
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<i>MECR</i> encodes mitochondrial trans-2-enoyl-coenzyme A-reductase (MECR); the transcript <a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_016011.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_016011.4</a> encodes a 373-amino acid protein (<a href="https://www.ncbi.nlm.nih.gov/protein/NP_057095.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_057095.4</a>) with four main domains: mitochondrial transit peptide, NADPH cofactor-binding domain, and two catalytic domains. MECR catalyzes the last step of human mitochondrial fatty acid synthesis (mtFAS), turning trans-2-enoyl-ACP into acyl-ACP. MECR also serves as the precursor for lipoic acid synthesis, which functions as a cofactor for key enzymes of the respiratory chain [<a class="bibr" href="#mecr-dis.REF.hiltunen.2009.9011" rid="mecr-dis.REF.hiltunen.2009.9011">Hiltunen et al 2009</a>].</p><p><b>Abnormal gene product.</b> Decreased MECR activity reduces production of octanoyl-ACP (which regulates mitochondrial RNA processing and translation) and reduces respiratory complex assembly [<a class="bibr" href="#mecr-dis.REF.kursu.2013.824" rid="mecr-dis.REF.kursu.2013.824">Kursu et al 2013</a>].</p></div><div id="mecr-dis.Chapter_Notes"><h2 id="_mecr-dis_Chapter_Notes_">Chapter Notes</h2><div id="mecr-dis.Author_Notes"><h3>Author Notes</h3><p>Dr Gali Heimer is a Senior Pediatric Neurologist and Director of the Angelman Clinic in the Pediatric Neurology Unit of the Edmond and Lily Safra Children's Hospital, and a member of the Talpiot Medical Leadership Program at the Sheba Medical Center.</p><p>Her clinical work and research focuses on neurogenetics: diagnosing known and novel genetic causes of rare neurologic diseases of childhood with emphasis on unraveling their pathomechanism and searching for therapeutic strategies.</p><p>The authors plan to test the effect of LA/C8 on cell lines from individuals with <i>MECR</i>-related neurologic disorder and – if favorable – to perform a clinical trial of LA/C8 supplementation. Clinicians are encouraged to contact the authors before initiating LA/C8 supplementation in an affected individual to obtain current dosing recommendations and to allow for prospective collection of clinical data pre- and post-treatment.</p></div><div id="mecr-dis.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>9 May 2019 (bp) Review posted live</div></li><li class="half_rhythm"><div>12 June 2017 (gh) Original submission</div></li></ul></div></div><div id="mecr-dis.References"><h2 id="_mecr-dis_References_">References</h2><div id="mecr-dis.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="mecr-dis.REF.heimer.2016.1229">Heimer G, Kerätär JM, Riley LG, Balasubramaniam S, Eyal E, Pietikäinen LP, Hiltunen JK, Marek-Yagel D, Hamada J, Gregory A, Rogers C, Hogarth P, Nance MA, Shalva N, Veber A, Tzadok M, Nissenkorn A, Tonduti D, Renaldo F, Kraoua I, Panteghini C, Valletta L, Garavaglia B, Cowley MJ, Gayevskiy V, Roscioli T, Silberstein JM, Hoffmann C, Raas-Rothschild A, Tiranti V, Anikster Y, Christodoulou J, Kastaniotis AJ, Ben-Zeev B, Hayflick SJ, et al. MECR mutations cause childhood-onset dystonia and optic atrophy, a mitochondrial fatty acid synthesis disorder. <span><span class="ref-journal">Am J Hum Genet. </span>2016;<span class="ref-vol">99</span>:1229–44.</span> [<a href="/pmc/articles/PMC5142118/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5142118</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27817865" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27817865</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mecr-dis.REF.hiltunen.2009.9011">Hiltunen JK, Schonauer MS, Autio KJ, Mittelmeier TM, Kastaniotis AJ, Dieckmann CL. Mitochondrial fatty acid synthesis type II: more than just fatty acids. <span><span class="ref-journal">J Biol Chem. </span>2009;<span class="ref-vol">284</span>:9011–5.</span> [<a href="/pmc/articles/PMC2666548/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2666548</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19028688" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19028688</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mecr-dis.REF.kursu.2013.824">Kursu VA, Pietikäinen LP, Fontanesi F, Aaltonen MJ, Suomi F, Raghavan Nair R, Schonauer MS, Dieckmann CL, Barrientos A, Hiltunen JK, Kastaniotis AJ. Defects in mitochondrial fatty acid synthesis result in failure of multiple aspects of mitochondrial biogenesis in Saccharomyces cerevisiae. <span><span class="ref-journal">Mol Microbiol. </span>2013;<span class="ref-vol">90</span>:824–40.</span> [<a href="/pmc/articles/PMC4153884/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4153884</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24102902" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24102902</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mecr-dis.REF.niezgoda.2013.785">Niezgoda J, Morgan PG. Anesthetic considerations in patients with mitochondrial defects. <span><span class="ref-journal">Paediatr Anaesth. </span>2013;<span class="ref-vol">23</span>:785–93.</span> [<a href="/pmc/articles/PMC3711963/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3711963</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23534340" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23534340</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mecr-dis.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></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK540959_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Gali Heimer</span>, MD, PhD<div class="affiliation small">Pediatric Neurology Unit, Safra Children's Hospital;<br />Pinchas Borenstein Talpiot Medical Leadership Program<br />Sheba Medical Center<br />Tel HaShomer, Israel</div><div class="affiliation small">The Sackler School of Medicine<br />Tel Aviv University<br />Tel Aviv, Israel<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.liamg@dm.hilag" class="oemail">moc.liamg@dm.hilag</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Allison Gregory</span>, MS<div class="affiliation small">Molecular and Medical Genetics<br />Oregon Health & Science University<br />Portland, Oregon<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.usho@ayrogerg" class="oemail">ude.usho@ayrogerg</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Penelope Hogarth</span>, MD<div class="affiliation small">Molecular and Medical Genetics<br />Oregon Health & Science University<br />Portland, Oregon<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.usho@phtragoh" class="oemail">ude.usho@phtragoh</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Susan Hayflick</span>, MD<div class="affiliation small">Molecular and Medical Genetics<br />Pediatrics and Neurology<br />Oregon Health & Science University<br />Portland, Oregon<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.usho@kcilfyah" class="oemail">ude.usho@kcilfyah</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Bruria Ben Zeev</span>, MD, Prof<div class="affiliation small">Pediatric Neurology Unit, Safra Children's Hospital<br />Sheba Medical Center<br />Tel HaShomer, Israel<br />The Sackler School of Medicine<br />Tel Aviv University<br />Tel Aviv, Israel<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="li.vog.htlaeh.abehs@veezneb.airurb" class="oemail">li.vog.htlaeh.abehs@veezneb.airurb</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">May 9, 2019</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. 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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>Heimer G, Gregory A, Hogarth P, et al. MECR-Related Neurologic Disorder. 2019 May 9. 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/mecp2-dup/?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/fg/?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="figobmecrdisTmoleculargenetictestinguse"><div id="mecr-dis.T.molecular_genetic_testing_use" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>MECR</i>-Related Neurologic Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK540959/table/mecr-dis.T.molecular_genetic_testing_use/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mecr-dis.T.molecular_genetic_testing_use_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mecr-dis.T.molecular_genetic_testing_use_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_mecr-dis.T.molecular_genetic_testing_use_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_mecr-dis.T.molecular_genetic_testing_use_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_mecr-dis.T.molecular_genetic_testing_use_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MECR</i>
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</td><td headers="hd_h_mecr-dis.T.molecular_genetic_testing_use_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_mecr-dis.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8/8 <sup>4</sup></td></tr><tr><td headers="hd_h_mecr-dis.T.molecular_genetic_testing_use_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_mecr-dis.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>6</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="mecr-dis.TF.1.1"><p class="no_margin">See <a href="/books/NBK540959/?report=reader#mecr-dis.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="mecr-dis.TF.1.2"><p class="no_margin">See <a href="#mecr-dis.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="mecr-dis.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="mecr-dis.TF.1.4"><p class="no_margin">n = 5 [<a class="bibr" href="#mecr-dis.REF.heimer.2016.1229" rid="mecr-dis.REF.heimer.2016.1229">Heimer et al 2016</a>]; n = 2 (families referred to the authors after the publication of <a class="bibr" href="#mecr-dis.REF.heimer.2016.1229" rid="mecr-dis.REF.heimer.2016.1229">Heimer et al 2016</a>); n = 1 [Author, personal communication]</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="mecr-dis.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="mecr-dis.TF.1.6"><p class="no_margin">No data on detection rate of gene-targeted deletion/duplication analysis are available.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmecrdisTdisorderswithdystoniaandm"><div id="mecr-dis.T.disorders_with_dystonia_and_m" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Disorders with Dystonia and MRI Signal Abnormality in the Basal Ganglia to Consider in the Differential Diagnosis of <i>MECR</i>-Related Neurologic Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK540959/table/mecr-dis.T.disorders_with_dystonia_and_m/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mecr-dis.T.disorders_with_dystonia_and_m_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" style="text-align:left;vertical-align:middle;">Differential Disorder</th><th id="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of Differential Disorder</th></tr><tr><th headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4" id="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/<i>MECR</i>-related neurologic disorder <sup>1</sup></th><th headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4" id="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from <i>MECR</i>-related neurologic disorder</th></tr></thead><tbody><tr><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Leigh syndrome<br />(See <a href="/books/n/gene/leigh-nucl-ov/?report=reader">Nuclear Gene-Encoded Leigh Syndrome Overview</a> & <a href="/books/n/gene/narp/?report=reader">Mitochondrial DNA-Associated Leigh Syndrome and NARP</a>.)</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 2.</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR, XL, Mit</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Optic atrophy may develop.</div></li><li class="half_rhythm"><div>Symptoms may worsen following febrile illness.</div></li></ul>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically seen:
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<ul><li class="half_rhythm"><div>Seizures, encephalopathy, cognitive regression</div></li><li class="half_rhythm"><div>↑ blood/CNS lactate</div></li></ul>
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May be seen on MRI:
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<ul><li class="half_rhythm"><div>Signal abnormality in brain stem in addition to basal ganglia lesions</div></li></ul>
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</td></tr><tr><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/lhon/?report=reader">Leber hereditary optic neuropathy</a>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 3.</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mit</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Optic atrophy is the main manifestation.</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Onset usually after 3rd decade (although childhood onset has been reported)</td></tr><tr><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Glutaric aciduria type 1<br />(OMIM <a href="https://omim.org/entry/231670" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">231670</a>)</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GCDH</i>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cognition may be preserved.</div></li><li class="half_rhythm"><div>Symptoms may worsen following febrile illness.</div></li></ul>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically seen:
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<ul><li class="half_rhythm"><div>Macrocephaly & widening of Sylvian fissures on MRI</div></li><li class="half_rhythm"><div>Episodes of acute encephalopathy w/dystonic crises</div></li><li class="half_rhythm"><div>↑ urine glutaric acid & 3-OH-glutaric acid</div></li></ul>
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</td></tr><tr><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">D-2-hydroxyglutaric aciduria<br />(OMIM <a href="https://omim.org/entry/609186" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">609186</a>)</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>D2HGDH</i>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Symptoms may worsen following febrile illness.</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically seen:
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<ul><li class="half_rhythm"><div>Seizures, cardiomyopathy, cognitive regression</div></li><li class="half_rhythm"><div>↑ urine D-2-hydroxyglutaric acid</div></li></ul>
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May be seen:
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<ul><li class="half_rhythm"><div>Subependymal cysts on MRI</div></li><li class="half_rhythm"><div>↑ blood/CNS lactate</div></li></ul>
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</td></tr><tr><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/bgd-biotin/?report=reader">Biotin-thiamine-responsive basal ganglia disease</a>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SLC19A3</i>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dysarthria & eye mvmt abnormality are common.</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically seen:
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<ul><li class="half_rhythm"><div>Encephalopathy</div></li><li class="half_rhythm"><div>Good response to high doses of biotin & thiamine</div></li></ul>
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May be seen:
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<ul><li class="half_rhythm"><div>Signal abnormality in the brain stem on MRI</div></li></ul>
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</td></tr><tr><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/huntington/?report=reader">Huntington disease</a>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>HTT</i> <sup>4</sup></td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ataxia & chorea may also be present.</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Characteristic MRI feature: caudate head atrophy</div></li><li class="half_rhythm"><div>Parkinsonism common in juvenile form</div></li></ul>
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</td></tr><tr><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/chac/?report=reader">Chorea-acanthocytosis</a>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>VPS13A</i>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dysarthria is common.</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically seen:
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<ul><li class="half_rhythm"><div>Onset after 3rd decade (although childhood onset has been reported)</div></li><li class="half_rhythm"><div>Cognitive & behavioral changes</div></li><li class="half_rhythm"><div>Caudate atrophy on MRI (characteristic feature)</div></li><li class="half_rhythm"><div>↑ creatine kinase & acanthocytes</div></li><li class="half_rhythm"><div>Seizures (in almost half of affected persons)</div></li></ul>
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</td></tr><tr><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/drpla/?report=reader">DRPLA</a> <sup>5</sup></td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ATN1</i>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ataxia & chorea may also be present.</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically seen:
|
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<ul><li class="half_rhythm"><div>Myoclonic epilepsy, behavioral changes, dementia</div></li><li class="half_rhythm"><div>Atrophic changes in cerebellum & brain stem on MRI</div></li></ul>
|
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</td></tr><tr><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/wilson/?report=reader">Wilson disease</a>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ATP7B</i>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Chorea & dysarthria are common.</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically seen:
|
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<ul><li class="half_rhythm"><div>Tremor, parkinsonism, behavioral changes</div></li><li class="half_rhythm"><div>Liver disease</div></li><li class="half_rhythm"><div>Kayser-Fleischer ring</div></li></ul>
|
|
May be seen:
|
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<ul><li class="half_rhythm"><div>Low serum ceruloplasmin & high urinary copper</div></li></ul>
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</td></tr><tr><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/nbia-ov/?report=reader">NBIA</a> <sup>6</sup></td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 7.</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR, AD, XL</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Dysarthria is common.</div></li><li class="half_rhythm"><div>Optic atrophy may be present.</div></li><li class="half_rhythm"><div>Hyperintense T<sub>2</sub>-weighted signal may be observed in basal ganglia on brain MRI.</div></li></ul>
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</td><td headers="hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_1_4 hd_h_mecr-dis.T.disorders_with_dystonia_and_m_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically seen:
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<ul><li class="half_rhythm"><div>Parkinsonism & neuropsychiatric abnormalities</div></li><li class="half_rhythm"><div>Brain iron accumulations & (in some cases) accompanying cerebral & cerebellar atrophy on MRI</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; Mit = mitochondrial; MOI = mode of inheritance; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="mecr-dis.TF.2.1"><p class="no_margin">In addition to dystonia and MRI findings of signal abnormality in the basal ganglia</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="mecr-dis.TF.2.2"><p class="no_margin">Leigh syndrome, a heterogeneous group of disorders, is associated with pathogenic variants in more than 70 genes (nuclear and mitochondrial).</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="mecr-dis.TF.2.3"><p class="no_margin">Pathogenic variants in <i>MT-ND1</i>, <i>MT-ND4</i>, and <i>MT-ND6</i> account for >90% of cases; pathogenic variants in other mitochondrial genes are also possible.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="mecr-dis.TF.2.4"><p class="no_margin">Huntington disease is caused by an expansion of 36 or more CAG trinucleotide repeats in <i>HTT</i>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="mecr-dis.TF.2.5"><p class="no_margin">DRPLA = dentatorubral-pallidoluysian atrophy</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="mecr-dis.TF.2.6"><p class="no_margin">NBIA = neurodegeneration with brain iron accumulation</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="mecr-dis.TF.2.7"><p class="no_margin">NBIA is a heterogeneous group of disorders associated with pathogenic variants in at least ten genes (see <a href="/books/n/gene/nbia-ov/?report=reader">Neurodegeneration with Brain Iron Accumulation Disorders Overview</a>).</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmecrdisTrecommendedevaluationsfollo"><div id="mecr-dis.T.recommended_evaluations_follo" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK540959/table/mecr-dis.T.recommended_evaluations_follo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mecr-dis.T.recommended_evaluations_follo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_mecr-dis.T.recommended_evaluations_follo_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_mecr-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Eyes</b>
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</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for optic atrophy & visual acuity</td></tr><tr><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gastrointestinal/</b>
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<br />
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<b>Feeding</b>
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</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterology / nutrition / feeding team eval</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Incl eval of aspiration risk & nutritional status</div></li><li class="half_rhythm"><div>Consider eval for gastric tube placement in patients w/dysphagia &/or aspiration risk.</div></li></ul>
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</td></tr><tr><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Musculoskeletal</b>
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</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OT & PT assessments</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess effect of mvmt disorder on activities of daily living</td></tr><tr><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" 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_mecr-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brain MRI</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Medication management for dystonia</div></li><li class="half_rhythm"><div>Rehab w/therapies & equipment needs assessment for dystonia, chorea, &/or ataxia</div></li></ul>
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</td></tr><tr><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Incl eval of motor, speech/language, general cognitive, & vocational skills</div></li><li class="half_rhythm"><div>Speech therapy & augmentative communication consultation for dysarthria</div></li></ul>
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</td></tr><tr><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neuropsychological</b>
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</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of cognitive function</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Miscellaneous/</b>
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<br />
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<b>Other</b>
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</td><td headers="hd_h_mecr-dis.T.recommended_evaluations_follo_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_mecr-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl genetic counseling</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">OT = occupational therapy; PT = physical therapy</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmecrdismolgenTA"><div id="mecr-dis.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>MECR-Related Neurologic Disorder: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK540959/table/mecr-dis.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mecr-dis.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_mecr-dis.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_mecr-dis.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_mecr-dis.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_mecr-dis.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_mecr-dis.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_mecr-dis.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/51102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>MECR</i>
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</a>
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</td><td headers="hd_b_mecr-dis.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=51102" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">1p35<wbr style="display:inline-block"></wbr>​.3</a>
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</td><td headers="hd_b_mecr-dis.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/Q9BV79" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Enoyl-[acyl-carrier-protein] reductase, mitochondrial</a>
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</td><td headers="hd_b_mecr-dis.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=MECR" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MECR</a>
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</td><td headers="hd_b_mecr-dis.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=MECR[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MECR</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="mecr-dis.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
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chromosome locus from
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmecrdismolgenTB"><div id="mecr-dis.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for MECR-Related Neurologic Disorder (<a href="/omim/608205,617282" 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/NBK540959/table/mecr-dis.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mecr-dis.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/608205" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">608205</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MITOCHONDRIAL TRANS-2-ENOYL-CoA REDUCTASE; MECR</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/617282" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">617282</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES; DYTOABG</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobmecrdisTmecrpathogenicvariantsdisc"><div id="mecr-dis.T.mecr_pathogenic_variants_disc" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p><i>MECR</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/NBK540959/table/mecr-dis.T.mecr_pathogenic_variants_disc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mecr-dis.T.mecr_pathogenic_variants_disc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mecr-dis.T.mecr_pathogenic_variants_disc_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_mecr-dis.T.mecr_pathogenic_variants_disc_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_mecr-dis.T.mecr_pathogenic_variants_disc_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_mecr-dis.T.mecr_pathogenic_variants_disc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.695G>A <sup>1</sup></td><td headers="hd_h_mecr-dis.T.mecr_pathogenic_variants_disc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly232Glu</td><td headers="hd_h_mecr-dis.T.mecr_pathogenic_variants_disc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_016011.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_016011<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_057095.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_057095<wbr style="display:inline-block"></wbr>​.4</a>
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</td></tr><tr><td headers="hd_h_mecr-dis.T.mecr_pathogenic_variants_disc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.830+2dupT <sup>1</sup></td><td headers="hd_h_mecr-dis.T.mecr_pathogenic_variants_disc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_mecr-dis.T.mecr_pathogenic_variants_disc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_016011.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_016011<wbr style="display:inline-block"></wbr>​.4</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><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 class="bkr_refwrap"><dt>1. </dt><dd><div id="mecr-dis.TF.4.1"><p class="no_margin">See <a href="#mecr-dis.Prevalence">Prevalence</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobmecrdisF1"><div id="mecr-dis.F1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK540959/bin/mecr-dis-Image001.jpg" alt="Figure 1. " /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>Magnetic resonance imaging of individuals with <i>MECR</i>-related neurologic disorder showing hyperintense T<sub>2</sub>-weighted and FLAIR signals within the basal ganglia</p><p>A. T<sub>2</sub>-weighted axial section demonstrating hyperintense pallidal signal (arrow) (Family G, Patient II:1) [Author, unpublished observation]</p><p>B. T<sub>2</sub>-weighted axial section demonstrating hyperintense signal in both pallidum and putamen (arrows) (Family G, Patient II:6) [Author, unpublished observation]</p><p>C. Flair axial section demonstrating hyperintense signal in both putamen and caudate (arrows) (Family C, Patient II:8) [<a class="bibr" href="#mecr-dis.REF.heimer.2016.1229" rid="mecr-dis.REF.heimer.2016.1229">Heimer et al 2016</a>]</p></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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