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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Glycogen Storage Disease Type IV - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="Glycogen Storage Disease Type IV">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2019/08/01">
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<meta name="citation_author" content="Pilar L Magoulas">
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<meta name="citation_author" content="Ayman W El-Hattab">
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<meta name="citation_keywords" content="Andersen Disease">
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<meta name="citation_keywords" content="Glycogen Branching Enzyme Deficiency">
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<meta name="citation_keywords" content="Glycogen Storage Disease IV">
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<meta name="citation_keywords" content="GSD IV">
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<meta name="citation_keywords" content="Glycogen Storage Disease IV">
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<meta name="citation_keywords" content="Glycogen Branching Enzyme Deficiency">
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<meta name="citation_keywords" content="Andersen Disease">
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<meta name="citation_keywords" content="GSD IV">
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<meta name="citation_keywords" content="1,4-alpha-glucan-branching enzyme">
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<meta name="DC.Title" content="Glycogen Storage Disease Type IV">
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<meta name="DC.Contributor" content="Ayman W El-Hattab">
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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="_NBK115333_"><span class="title" itemprop="name">Glycogen Storage Disease Type IV</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: Andersen Disease, Glycogen Branching Enzyme Deficiency, Glycogen Storage Disease IV, GSD IV</div><p class="contribs">Magoulas PL, El-Hattab AW.</p><p class="fm-aai"><a href="#_NBK115333_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 20 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="gsd4.Summary" itemprop="description"><h2 id="_gsd4_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>The clinical manifestations of glycogen storage disease type IV (GSD IV) discussed in this entry span a continuum of different subtypes with variable ages of onset, severity, and clinical features. Clinical findings vary extensively both within and between families.</p><ul><li class="half_rhythm"><div>The <i>fatal perinatal neuromuscular subtype</i> presents in utero with fetal akinesia deformation sequence, including decreased fetal movements, polyhydramnios, and fetal hydrops. Death usually occurs in the neonatal period.</div></li><li class="half_rhythm"><div>The <i>congenital neuromuscular subtype</i> presents in the newborn period with profound hypotonia, respiratory distress, and dilated cardiomyopathy. Death usually occurs in early infancy.</div></li><li class="half_rhythm"><div>Infants with the <i>classic (progressive) hepatic subtype</i> may appear normal at birth, but rapidly develop failure to thrive; hepatomegaly, liver dysfunction, and progressive liver cirrhosis; hypotonia; and cardiomyopathy. Without liver transplantation, death from liver failure usually occurs by age five years.</div></li><li class="half_rhythm"><div>Children with the <i>non-progressive hepatic subtype</i> tend to present with hepatomegaly, liver dysfunction, myopathy, and hypotonia; however, they are likely to survive without progression of the liver disease and may not show cardiac, skeletal muscle, or neurologic involvement.</div></li><li class="half_rhythm"><div>The <i>childhood neuromuscular subtype</i> is rare and the course is variable, ranging from onset in the second decade with a mild disease course to a more severe, progressive course resulting in death in the third decade.</div></li></ul></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis is established in a proband by the demonstration of glycogen branching enzyme (GBE) deficiency in liver, muscle, or skin fibroblasts or the identification of biallelic pathogenic variants in <i>GBE1</i> on molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Management should involve a multidisciplinary team including specialists in hepatology, neurology, nutrition, medical or biochemical genetics, and child development. Liver transplantation is the only treatment option for individuals with the progressive hepatic subtype of GSD IV who develop liver failure; however, the risk for morbidity and mortality is high, in part because of the extrahepatic manifestations of GSD type IV, especially cardiomyopathy. Children with skeletal myopathy and/or hypotonia warrant developmental evaluation and physical therapy as needed. Those with cardiomyopathy warrant care by a cardiologist. Heart transplant may be an option in individuals with severe cardiac involvement.</p><p><i>Prevention of secondary complications:</i> Prevent nutritional deficiencies (e.g., of fat-soluble vitamins) by ensuring adequate dietary intake; prevent perioperative bleeding by assessment of a coagulation profile and use of fresh frozen plasma as needed.</p><p><i>Surveillance:</i> No clinical guidelines for surveillance are available. The following evaluations are suggested (with frequency varying according to disease severity): liver function tests including liver transaminases, albumin, and coagulation profile (PT and PTT); abdominal ultrasound examination; echocardiogram; neurologic assessment; nutritional assessment. If cardiomyopathy was not observed on baseline screening echocardiogram at the time of initial diagnosis, repeat echocardiograms every three months during infancy, every six months during early childhood, and annually thereafter.</p><p><i>Evaluation of relatives at risk:</i> If the <i>GBE1</i> pathogenic variants have been identified in an affected family member, test at-risk relatives to allow for early diagnosis and management of disease manifestations.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>GSD IV is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Although affected sibs are expected to manifest the same subtype of GSD IV, the age of onset and presentation may differ. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible based on molecular testing if the pathogenic variants in the family have been identified. If the pathogenic variants have not been identified, GBE testing on cultured amniocytes can be performed for prenatal diagnosis.</p></div></div><div id="gsd4.Diagnosis"><h2 id="_gsd4_Diagnosis_">Diagnosis</h2><p>The diagnosis of glycogen storage disease type IV (GSD IV) is suspected based on the clinical presentation and the finding of abnormally branched glycogen accumulation in muscle or liver tissue. The diagnosis is confirmed by the demonstration of glycogen branching enzyme (GBE) deficiency in liver, muscle, or skin fibroblasts [<a class="bibr" href="#gsd4.REF.brown.1983.636" rid="gsd4.REF.brown.1983.636">Brown & Brown 1983</a>], and/or the identification of biallelic pathogenic variants in <i>GBE1</i>.</p><div id="gsd4.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Glycogen storage disease type IV (GSD IV) <b>should be suspected</b> in individuals with the features below. While subtypes with variable ages of onset, severity, and clinical features have been recognized, the GSD IV phenotype represents a continuum that ranges from mild to severe [<a class="bibr" href="#gsd4.REF.burrow.2006.878" rid="gsd4.REF.burrow.2006.878">Burrow et al 2006</a>].</p><p><b>Clinical features</b> by subtype:</p><ul><li class="half_rhythm"><div><b>Fatal perinatal neuromuscular subtype.</b> Decreased fetal movements, polyhydramnios, and fetal hydrops that may be detected prenatally; arthrogryposis, severe hypotonia, muscle atrophy at birth, early neonatal death</div></li><li class="half_rhythm"><div><b>Congenital neuromuscular subtype.</b> Profound neonatal hypotonia at birth, respiratory failure, dilated cardiomyopathy, early infantile death</div></li><li class="half_rhythm"><div><b>Classic (progressive) hepatic subtype.</b> Failure to thrive, hepatomegaly, liver dysfunction, progressive liver cirrhosis with portal hypertension, ascites, and esophageal varices, hypotonia, and cardiomyopathy; death typically by age five years from liver failure</div></li><li class="half_rhythm"><div><b>Non-progressive hepatic subtype.</b> Liver dysfunction, myopathy, and hypotonia in childhood</div></li><li class="half_rhythm"><div><b>Childhood neuromuscular subtype.</b> Chronic, progressive myopathy; dilated cardiomyopathy in some individuals</div></li></ul><p>
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<b>Laboratory features</b>
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</p><ul><li class="half_rhythm"><div><b>Liver enzymes</b> typically elevated in the hepatic subtypes</div></li><li class="half_rhythm"><div>
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<b>Hypoalbuminemia</b>
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</div></li><li class="half_rhythm"><div>Prolonged <b>partial thromboplastin time</b> (PTT) and <b>prothrombin time</b> (PT) with progressive deterioration of liver function</div></li></ul><p><b>Imaging features.</b> Abdominal ultrasound examination typically reveals enlarged liver with signs of fibrosis or cirrhosis.</p><p><b>Histopathology</b> of affected tissues (e.g., liver, heart, muscle) reveals:</p><ul><li class="half_rhythm"><div>Markedly enlarged hepatocytes that contain periodic acid-Schiff (PAS)-positive and diastase-resistant inclusions, features characteristic of the abnormally branched glycogen found in GSD IV. Widespread infiltrates of foamy histiocytes with intra-cytoplasmic deposits within the reticuloendothelial system (RES) have been reported [<a class="bibr" href="#gsd4.REF.magoulas.2012.943" rid="gsd4.REF.magoulas.2012.943">Magoulas et al 2012</a>]. Interstitial fibrosis with wide fibrous septa and distorted hepatic architecture are observed [<a class="bibr" href="#gsd4.REF.moses.2002.177" rid="gsd4.REF.moses.2002.177">Moses & Parvari 2002</a>].</div></li><li class="half_rhythm"><div>On electron microscopy, fine fibrillary aggregates of electron-dense amylopectin-like material within the cytoplasm of hepatocytes in some individuals.</div></li></ul></div><div id="gsd4.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of glycogen storage disease type IV (GSD IV) <b>is established</b> in a proband by the presence of the above <a href="#gsd4.Suggestive_Findings">suggestive findings</a> AND identification of:</p><ul><li class="half_rhythm"><div>Reduced glycogen branching enzyme (GBE) activity (most commonly assayed in cultured skin fibroblasts but may also be assayed in muscle or liver tissue); OR</div></li><li class="half_rhythm"><div>Biallelic pathogenic variants in <i>GBE1</i> on molecular genetic testing (see <a href="/books/NBK115333/table/gsd4.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobgsd4Tmoleculargenetictestingusedin">Table 1</a>).</div></li></ul><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing, multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, exome array, genome sequencing) depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of GSD IV is broad, individuals with the distinctive findings described in <a href="#gsd4.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#gsd4.Option_1">Option 1</a>), whereas those with a phenotype indistinguishable from many other inherited disorders with liver dysfunction and/or cardiomyopathy are more likely to be diagnosed using genomic testing (see <a href="#gsd4.Option_2">Option 2</a>).</p><div id="gsd4.Option_1"><h4>Option 1</h4><p>When the phenotypic and laboratory findings suggest the diagnosis of GSD IV, 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>GBE1</i> detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If only one or no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> that includes <i>GBE1</i> and other genes of interest (see <a href="#gsd4.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see <a href="/books/NBK115333/table/gsd4.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobgsd4Tmoleculargenetictestingusedin">Table 1</a>).</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="gsd4.Option_2"><h4>Option 2</h4><p>When the phenotype is indistinguishable from many other inherited disorders characterized by liver dysfunction, <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. In addition, many laboratories now offer rapid or critical exome sequencing, which can provide results within a shorter time frame, and thus potentially provide an earlier diagnosis and guide management or treatment decisions.</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.</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="figgsd4Tmoleculargenetictestingusedin"><a href="/books/NBK115333/table/gsd4.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobgsd4Tmoleculargenetictestingusedin"><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="gsd4.T.molecular_genetic_testing_used_in"><a href="/books/NBK115333/table/gsd4.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobgsd4Tmoleculargenetictestingusedin">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Glycogen Storage Disease Type IV </p></div></div></div></div></div><div id="gsd4.Clinical_Characteristics"><h2 id="_gsd4_Clinical_Characteristics_">Clinical Characteristics</h2><div id="gsd4.Clinical_Description"><h3>Clinical Description</h3><p>The clinical manifestations of glycogen storage disease type IV (GSD IV) span a continuum from mild to severe [<a class="bibr" href="#gsd4.REF.burrow.2006.878" rid="gsd4.REF.burrow.2006.878">Burrow et al 2006</a>]. Within this continuum several different subtypes with variable age of onset, severity, and clinical features have been recognized. While prognosis tends to depend on the subtype of GSD IV, clinical findings vary extensively both within and between families.</p><p>The <b>fatal perinatal neuromuscular subtype</b>, the most severe subtype, presents in utero with fetal akinesia deformation sequence, including decreased fetal movements, polyhydramnios, and fetal hydrops. Newborns may have arthrogryposis, severe hypotonia, and muscular atrophy, often resembling infants with the severe forms of <a href="/books/n/gene/sma/?report=reader">spinal muscular atrophy</a> [<a class="bibr" href="#gsd4.REF.tay.2004.253" rid="gsd4.REF.tay.2004.253">Tay et al 2004</a>]. Death usually occurs in the neonatal period, frequently as a result of cardiopulmonary compromise.</p><p>The <b>congenital neuromuscular subtype</b> presents in the newborn period with profound hypotonia, respiratory distress, dilated cardiomyopathy, and death in early infancy typically from cardiopulmonary compromise [<a class="bibr" href="#gsd4.REF.moses.2002.177" rid="gsd4.REF.moses.2002.177">Moses & Parvari 2002</a>]. <a class="bibr" href="#gsd4.REF.li.2012.204" rid="gsd4.REF.li.2012.204">Li et al [2012]</a> recently reported two unrelated infants with this subtype of GSD IV who were also small for gestational age. Both died between ages two and three months.</p><p>The <b>hepatic subtype</b>, the most common presentation of GSD IV, can be classified as either progressive (classic) or non-progressive.</p><ul><li class="half_rhythm"><div>In the <b>progressive</b> hepatic subtype, children may appear normal at birth, but then rapidly deteriorate in the first few months of life with failure to thrive, hepatomegaly, and elevated liver enzymes. This stage is typically followed by progressive liver dysfunction and cirrhosis with hypoalbuminemia, prolonged partial thromboplastin time (PTT) and prothrombin time (PT), portal hypertension, ascites, and esophageal varices. Muscle tone, often normal at the time of diagnosis, progresses to generalized hypotonia within the first one to two years of life [<a class="bibr" href="#gsd4.REF.magoulas.2012.943" rid="gsd4.REF.magoulas.2012.943">Magoulas et al 2012</a>]. Without liver transplantation, death from liver failure usually occurs by age five years [<a class="bibr" href="#gsd4.REF.chen.2001" rid="gsd4.REF.chen.2001">Chen 2001</a>, <a class="bibr" href="#gsd4.REF.moses.2002.177" rid="gsd4.REF.moses.2002.177">Moses & Parvari 2002</a>]. Dilated cardiomyopathy and progressive cardiac failure, reported to occur following orthotopic liver transplantation, have resulted in death [<a class="bibr" href="#gsd4.REF.sokal.1992.200" rid="gsd4.REF.sokal.1992.200">Sokal et al 1992</a>, <a class="bibr" href="#gsd4.REF.rosenthal.1995.373" rid="gsd4.REF.rosenthal.1995.373">Rosenthal et al 1995</a>].</div></li><li class="half_rhythm"><div>In the less common <b>non-progressive</b> hepatic subtype, presentation can be in childhood with hepatomegaly, liver dysfunction, myopathy, and hypotonia. These individuals tend to survive without evidence of progression of the liver disease [<a class="bibr" href="#gsd4.REF.moses.2002.177" rid="gsd4.REF.moses.2002.177">Moses & Parvari 2002</a>]. They also may not show cardiac, skeletal muscle, or neurologic involvement. Liver enzymes are usually abnormal in childhood at the time of presentation, but subsequently may return to (and remain) normal [<a class="bibr" href="#gsd4.REF.mcconkierosell.1996.51" rid="gsd4.REF.mcconkierosell.1996.51">McConkie-Rosell et al 1996</a>].</div></li></ul><p>The <b>childhood neuromuscular subtype</b> of GSD IV is rare [<a class="bibr" href="#gsd4.REF.reusche.1992.36" rid="gsd4.REF.reusche.1992.36">Reusche et al 1992</a>, <a class="bibr" href="#gsd4.REF.schr_der.1993.419" rid="gsd4.REF.schr_der.1993.419">Schröder et al 1993</a>]. Individuals typically present in the second decade and may have mild-to-severe myopathy and dilated cardiomyopathy. The natural history is variable: some individuals have a mild disease course throughout life while others have a more severe, progressive course resulting in death in the third decade.</p></div><div id="gsd4.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>Genotype-phenotype correlations remain unclear, but are emerging [<a class="bibr" href="#gsd4.REF.ziemssen.2000.536" rid="gsd4.REF.ziemssen.2000.536">Ziemssen et al 2000</a>, <a class="bibr" href="#gsd4.REF.magoulas.2012.943" rid="gsd4.REF.magoulas.2012.943">Magoulas et al 2012</a>].</p><ul><li class="half_rhythm"><div>Individuals with the perinatal and congenital subtypes tend to have two null variants, including nonsense, frameshift, and splice site variants leading to premature truncation of the protein likely resulting in complete absence of glycogen branching enzyme (GBE) activity;</div></li><li class="half_rhythm"><div>Individuals with the classic hepatic subtype tend to be compound heterozygotes for a null and a missense variant.</div></li></ul><p>These generalizations notwithstanding, considerable overlap exists both between and within the subtypes of GSD IV [<a class="bibr" href="#gsd4.REF.li.2010.s83" rid="gsd4.REF.li.2010.s83">Li et al 2010</a>].</p></div><div id="gsd4.Nomenclature"><h3>Nomenclature</h3><p>Glycogen storage disease type IV was referred to as glycogenosis IV in early publications.</p></div><div id="gsd4.Prevalence"><h3>Prevalence</h3><p>Glycogen storage disease type IV is rare, accounting for approximately 3% of the glycogen storage diseases [<a class="bibr" href="#gsd4.REF.chen.2001" rid="gsd4.REF.chen.2001">Chen 2001</a>] for an overall incidence of approximately 1:600,000-1:800,000.</p><p>To date, more than 50 individuals with molecularly confirmed GSD IV have been reported [<a class="bibr" href="#gsd4.REF.fernandez.2010.269" rid="gsd4.REF.fernandez.2010.269">Fernandez et al 2010</a>, <a class="bibr" href="#gsd4.REF.li.2010.s83" rid="gsd4.REF.li.2010.s83">Li et al 2010</a>, <a class="bibr" href="#gsd4.REF.li.2012.204" rid="gsd4.REF.li.2012.204">Li et al 2012</a>, <a class="bibr" href="#gsd4.REF.magoulas.2012.943" rid="gsd4.REF.magoulas.2012.943">Magoulas et al 2012</a>, <a class="bibr" href="#gsd4.REF.mochel.2012.433" rid="gsd4.REF.mochel.2012.433">Mochel et al 2012</a>, <a class="bibr" href="#gsd4.REF.ravenscroft.2013.165" rid="gsd4.REF.ravenscroft.2013.165">Ravenscroft et al 2013</a>, <a class="bibr" href="#gsd4.REF.paradas.2014.41" rid="gsd4.REF.paradas.2014.41">Paradas at al 2014</a>, <a class="bibr" href="#gsd4.REF.akman.2015.441" rid="gsd4.REF.akman.2015.441">Akman et al 2015</a>, <a class="bibr" href="#gsd4.REF.sampaolo.2015.247" rid="gsd4.REF.sampaolo.2015.247">Sampaolo et al 2015</a>, <a class="bibr" href="#gsd4.REF.bendrothasmussen.2016.38" rid="gsd4.REF.bendrothasmussen.2016.38">Bendroth-Asmussen et al 2016</a>, <a class="bibr" href="#gsd4.REF.dainese.2016.512" rid="gsd4.REF.dainese.2016.512">Dainese et al 2016</a>, <a class="bibr" href="#gsd4.REF.francopalacios.2016.4092" rid="gsd4.REF.francopalacios.2016.4092">Franco-Palacios et al 2016</a>, <a class="bibr" href="#gsd4.REF.said.2016.152" rid="gsd4.REF.said.2016.152">Said et al 2016</a>, <a class="bibr" href="#gsd4.REF.iijima.2018.31" rid="gsd4.REF.iijima.2018.31">Iijima et al 2018</a>].</p></div></div><div id="gsd4.Genetically_Related_Allelic_Disorde"><h2 id="_gsd4_Genetically_Related_Allelic_Disorde_">Genetically Related (Allelic) Disorders</h2><p>Adult-onset polyglucosan body disease (APBD) is the only other phenotype known to be associated with mutation of <i>GBE1</i> (see <a href="/books/n/gene/apbd/?report=reader">Adult Polyglucosan Body Disease</a>). APBD is characterized by adult-onset progressive neurogenic bladder, gait difficulties (i.e., spasticity and weakness) resulting from mixed upper- and lower-motor neuron involvement, sensory loss predominantly in the distal lower extremities, and mild cognitive difficulties (often executive dysfunction). In APBD, GBE activity is reduced or normal. Affected individuals are either homozygous or compound heterozygous for a pathogenic missense variant in <i>GBE1</i> including <a href="/books/NBK115333/table/gsd4.T.notable_gbe1_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobgsd4Tnotablegbe1pathogenicvariants">p.Tyr329Ser</a>, <a href="/books/NBK115333/table/gsd4.T.notable_gbe1_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobgsd4Tnotablegbe1pathogenicvariants">p.Arg515His</a>, and <a href="/books/NBK115333/table/gsd4.T.notable_gbe1_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobgsd4Tnotablegbe1pathogenicvariants">p.Arg524Gln</a> [<a class="bibr" href="#gsd4.REF.lossos.1998.867" rid="gsd4.REF.lossos.1998.867">Lossos et al 1998</a>, <a class="bibr" href="#gsd4.REF.ziemssen.2000.536" rid="gsd4.REF.ziemssen.2000.536">Ziemssen et al 2000</a>, <a class="bibr" href="#gsd4.REF.klein.2004.323" rid="gsd4.REF.klein.2004.323">Klein et al 2004</a>]. Inheritance is autosomal recessive.</p></div><div id="gsd4.Differential_Diagnosis"><h2 id="_gsd4_Differential_Diagnosis_">Differential Diagnosis</h2><div id="gsd4.Perinatal_and_Congenital_Neuromuscu"><h3>Perinatal and Congenital Neuromuscular Subtypes of GSD IV</h3><p>The differential diagnosis of the perinatal and congenital neuromuscular subtypes of GSD IV includes the disorders summarized in <a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di/?report=objectonly" target="object" rid-ob="figobgsd4Tothergenesofinterestinthedi">Table 2a</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgsd4Tothergenesofinterestinthedi"><a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di/?report=objectonly" target="object" title="Table 2a. " class="img_link icnblk_img" rid-ob="figobgsd4Tothergenesofinterestinthedi"><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="gsd4.T.other_genes_of_interest_in_the_di"><a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di/?report=objectonly" target="object" rid-ob="figobgsd4Tothergenesofinterestinthedi">Table 2a. </a></h4><p class="float-caption no_bottom_margin">Other Genes of Interest in the Differential Diagnosis of Perinatal and Congenital Neuromuscular Subtypes of GSD IV </p></div></div></div><div id="gsd4.Classic_Hepatic_Subtype_of_GSD_IV"><h3>Classic Hepatic Subtype of GSD IV</h3><p>The differential diagnosis of the classic hepatic subtype of GSD IV includes other glycogen storage disorders and mitochondrial DNA depletion syndromes. Examples of these categories of disorders are described in <a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di_1/?report=objectonly" target="object" rid-ob="figobgsd4Tothergenesofinterestinthedi1">Table 2b</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgsd4Tothergenesofinterestinthedi1"><a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di_1/?report=objectonly" target="object" title="Table 2b. " class="img_link icnblk_img" rid-ob="figobgsd4Tothergenesofinterestinthedi1"><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="gsd4.T.other_genes_of_interest_in_the_di_1"><a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di_1/?report=objectonly" target="object" rid-ob="figobgsd4Tothergenesofinterestinthedi1">Table 2b. </a></h4><p class="float-caption no_bottom_margin">Other Genes of Interest in the Differential Diagnosis of the Classic Hepatic Subtype of GSD IV </p></div></div></div><div id="gsd4.Childhood_Neuromuscular_Subtype_of"><h3>Childhood Neuromuscular Subtype of GSD IV</h3><p>The differential diagnosis of the childhood neuromuscular subtype of GSD IV includes <a href="/books/n/gene/mt-overview/?report=reader">mitochondrial myopathies</a> and the disorders summarized in <a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di_2/?report=objectonly" target="object" rid-ob="figobgsd4Tothergenesofinterestinthedi2">Table 2c</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgsd4Tothergenesofinterestinthedi2"><a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di_2/?report=objectonly" target="object" title="Table 2c. " class="img_link icnblk_img" rid-ob="figobgsd4Tothergenesofinterestinthedi2"><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="gsd4.T.other_genes_of_interest_in_the_di_2"><a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di_2/?report=objectonly" target="object" rid-ob="figobgsd4Tothergenesofinterestinthedi2">Table 2c. </a></h4><p class="float-caption no_bottom_margin">Other Genes of Interest in the Differential Diagnosis of the Childhood Neuromuscular Subtype of GSD IV </p></div></div></div></div><div id="gsd4.Management"><h2 id="_gsd4_Management_">Management</h2><div id="gsd4.Evaluations_Following_Initial_Diagn"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with glycogen storage disease type IV (GSD IV), the evaluations summarized in <a href="/books/NBK115333/table/gsd4.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobgsd4Trecommendedevaluationsfollowing">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="figgsd4Trecommendedevaluationsfollowing"><a href="/books/NBK115333/table/gsd4.T.recommended_evaluations_following/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobgsd4Trecommendedevaluationsfollowing"><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="gsd4.T.recommended_evaluations_following"><a href="/books/NBK115333/table/gsd4.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobgsd4Trecommendedevaluationsfollowing">Table 3. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with Glycogen Storage Disease Type IV </p></div></div></div><div id="gsd4.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Management should involve a multidisciplinary team including specialists in hepatology, neurology, nutrition, medical or biochemical genetics, and child development.</p><div id="gsd4.Hepatic_Manifestations"><h4>Hepatic Manifestations</h4><p>Liver transplantation is the only treatment option for individuals with the progressive hepatic subtype of GSD IV who develop liver failure. Of the 20 individuals with GSD IV who have received a liver transplant to date, two required a second liver transplant and six died: four from sepsis, one from hepatic artery thrombosis, and one from cardiomyopathy. The prognosis in persons with GSD IV who undergo liver transplantation is poor because of the significant risk for morbidity and mortality, which is in part attributed to the extrahepatic manifestations of GSD type IV, especially cardiomyopathy [<a class="bibr" href="#gsd4.REF.davis.2008.137" rid="gsd4.REF.davis.2008.137">Davis & Weinstein 2008</a>, <a class="bibr" href="#gsd4.REF.magoulas.2012.943" rid="gsd4.REF.magoulas.2012.943">Magoulas et al 2012</a>, <a class="bibr" href="#gsd4.REF.troisi.2014.354" rid="gsd4.REF.troisi.2014.354">Troisi et al 2014</a>, <a class="bibr" href="#gsd4.REF.choi.2018.365" rid="gsd4.REF.choi.2018.365">Choi et al 2018</a>].</p><p>Selecting appropriate candidates for liver transplantation can be complex. Histologic, molecular, or clinical predictors of disease progression are likely to be useful in stratifying patients prior to liver transplantation [<a class="bibr" href="#gsd4.REF.davis.2008.137" rid="gsd4.REF.davis.2008.137">Davis & Weinstein 2008</a>]. Factors such as glycogen branching enzyme (GBE) activity may not be the best predictor of outcome since the level of GBE activity in different tissues can vary by disease subtype and severity.</p></div><div id="gsd4.Neurologic_Manifestations"><h4>Neurologic Manifestations</h4><p>Children with skeletal myopathy and/or hypotonia who experience motor developmental delay warrant developmental evaluation and physical therapy as needed.</p></div><div id="gsd4.Cardiac_Manifestations"><h4>Cardiac Manifestations</h4><p>For those with cardiomyopathy, care by a cardiologist is warranted. Individuals with severe cardiomyopathy secondary to glycogenosis may be candidates for cardiac transplantation [<a class="bibr" href="#gsd4.REF.ewert.1999.850" rid="gsd4.REF.ewert.1999.850">Ewert et al 1999</a>]; however, consideration of potential contraindications to cardiac transplantation, including myopathy, liver failure, and cachexia, is essential before pursuing this treatment option.</p></div></div><div id="gsd4.Prevention_of_Secondary_Complicatio"><h3>Prevention of Secondary Complications</h3><p>Nutritional deficiencies (e.g., of fat-soluble vitamins) can be prevented by ensuring adequate dietary intake based on frequent assessments by and recommendations of a dietitian experienced in managing children with liver disease.</p><p>Bleeding due to coagulopathy can occur especially with surgical procedures; therefore, it is recommended that a coagulation profile be assessed before surgical procedures and fresh frozen plasma be given preoperatively as needed.</p></div><div id="gsd4.Surveillance"><h3>Surveillance</h3><p>No clinical guidelines for surveillance are available.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgsd4Trecommendedsurveillanceforindi"><a href="/books/NBK115333/table/gsd4.T.recommended_surveillance_for_indi/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobgsd4Trecommendedsurveillanceforindi"><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="gsd4.T.recommended_surveillance_for_indi"><a href="/books/NBK115333/table/gsd4.T.recommended_surveillance_for_indi/?report=objectonly" target="object" rid-ob="figobgsd4Trecommendedsurveillanceforindi">Table 4. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with Glycogen Storage Disease Type IV </p></div></div></div><div id="gsd4.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>If the <i>GBE1</i> pathogenic variants have been identified in an affected family member, at-risk relatives can be tested so that those with the pathogenic variants can be evaluated for involvement of the liver, skeletal muscle, and heart to allow for early diagnosis and management of disease manifestations.</p><p>See <a href="#gsd4.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="gsd4.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="http://www.clinicaltrials.gov" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="http://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="gsd4.Genetic_Counseling"><h2 id="_gsd4_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="gsd4.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Glycogen storage disease type IV (GSD IV) is inherited in an autosomal recessive manner.</p></div><div id="gsd4.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>GBE1</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>Affected sibs are expected to manifest the same subtype of GSD IV; however, age of onset and presentation may differ.</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> The offspring of an individual with GSD IV are obligate heterozygotes (carriers) for a pathogenic variant in <i>GBE1</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 a <i>GBE1</i> pathogenic variant.</p></div><div id="gsd4.Carrier_Detection"><h3>Carrier Detection</h3><p><b>Molecular genetic testing.</b> Molecular genetic testing is the preferred method for determining an individual's carrier status. Carrier testing for at-risk family members requires prior identification of the <i>GBE1</i> pathogenic variants in the family.</p><p><b>Biochemical genetic testing.</b> Analysis of glycogen branching enzyme (GBE) activity alone is not sufficient to determine carrier status since enzyme activity in carriers may be within the normal range.</p></div><div id="gsd4.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#gsd4.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><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><p><b>DNA banking</b> is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.</p></div><div id="gsd4.Prenatal_Testing_and_Preimplantatio"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p><b>Molecular genetic testing.</b> Once the <i>GBE1</i> pathogenic variants have been identified in an affected family member, molecular genetic prenatal testing for the familial <i>GBE1</i> pathogenic variants and preimplantation genetic testing are possible.</p><p><b>Biochemical genetic testing.</b> Prenatal testing is possible by analysis of glycogen branching enzyme (GBE) activity in amniocytes or cultured chorionic villi obtained by amniocentesis usually performed at approximately 15 to 18 weeks' gestation or chorionic villus sampling (CVS) at approximately ten to 12 weeks' gestation.</p><p>Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.</p></div></div><div id="gsd4.Resources"><h2 id="_gsd4_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>Association for Glycogen Storage Disease</b>
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</div><div>
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<a href="http://www.agsdus.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.agsdus.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Association for Glycogen Storage Disease UK (AGSD-UK)</b>
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</div><div>9 Lindop Road</div><div>Altrincham Cheshire WA15 9DZ</div><div>United Kingdom</div><div><b>Phone:</b> 0161 980 7303</div><div>
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<a href="http://www.agsd.org.uk" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.agsd.org.uk</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Library of Medicine Genetics Home Reference</b>
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</div><div>
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<a href="https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iv" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Glycogen storage disease type IV</a>
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</div></li><li class="half_rhythm"><div>
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<b>European Reference Network for Hereditary Metabolic Disorders (MetabERN)</b>
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</div><div>
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<a href="https://metab.ern-net.eu/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MetabERN</a>
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</div></li><li class="half_rhythm"><div>
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<b>Metabolic Support UK</b>
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</div><div>United Kingdom</div><div><b>Phone:</b> 0845 241 2173</div><div>
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<a href="https://metabolicsupportuk.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">metabolicsupportuk.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>EUROMAC</b>
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</div><div>Spain</div><div>
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<a href="https://www.euromacregistry.eu/portal1/h_index.php" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.euromacregistry.eu</a>
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</div></li></ul>
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</div><div id="gsd4.Molecular_Genetics"><h2 id="_gsd4_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="figgsd4molgenTA"><a href="/books/NBK115333/table/gsd4.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobgsd4molgenTA"><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="gsd4.molgen.TA"><a href="/books/NBK115333/table/gsd4.molgen.TA/?report=objectonly" target="object" rid-ob="figobgsd4molgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Glycogen Storage Disease Type IV: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgsd4molgenTB"><a href="/books/NBK115333/table/gsd4.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobgsd4molgenTB"><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="gsd4.molgen.TB"><a href="/books/NBK115333/table/gsd4.molgen.TB/?report=objectonly" target="object" rid-ob="figobgsd4molgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Glycogen Storage Disease Type IV (View All in OMIM) </p></div></div><div id="gsd4.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>Glycogen branching enzyme (GBE), a 702-amino acid protein, catalyzes the transfer of alpha-1,4-linked glucosyl units from the outer end of a glycogen chain to an alpha-1,6 position on the same or a neighboring glycogen chain. Branching of the chains is essential to increase the solubility of the glycogen molecule and, consequently, reduce the osmotic pressure within cells [<a class="bibr" href="#gsd4.REF.thon.1993.7509" rid="gsd4.REF.thon.1993.7509">Thon et al 1993</a>]. The GBE protein contains two highly conserved domains at the N- and C-terminals with sequences similar to isoamylase (glycoside hydrolase) and alpha-amylase, respectively. These two domains flank the alpha-amylase catalytic domain that encompasses the central portion of the enzyme [<a class="bibr" href="#gsd4.REF.moses.2002.177" rid="gsd4.REF.moses.2002.177">Moses & Parvari 2002</a>].</p><p>The underlying molecular defects in <i>GBE1</i> lead to the production of little or no functional GBE, resulting in abnormally formed glycogen (with fewer branch points and longer unbranched outer chains) with an amylopectin-like structure that accumulates in various tissues, most commonly the liver, heart, muscle, brain, spinal cord, peripheral nerve, and skin [<a class="bibr" href="#gsd4.REF.thon.1993.7509" rid="gsd4.REF.thon.1993.7509">Thon et al 1993</a>, <a class="bibr" href="#gsd4.REF.chen.2001" rid="gsd4.REF.chen.2001">Chen 2001</a>, <a class="bibr" href="#gsd4.REF.moses.2002.177" rid="gsd4.REF.moses.2002.177">Moses & Parvari 2002</a>]. It has been postulated that alteration in the glycogen branching structure that makes it less soluble may result in a foreign body reaction that leads to the tissue injury and dysfunction observed in GSD IV [<a class="bibr" href="#gsd4.REF.howell.1991.55" rid="gsd4.REF.howell.1991.55">Howell 1991</a>]; however, the specific pathogenic mechanisms remain unknown.</p><p><b>Mechanism of disease causation.</b> Loss of function.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgsd4Tnotablegbe1pathogenicvariants"><a href="/books/NBK115333/table/gsd4.T.notable_gbe1_pathogenic_variants/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobgsd4Tnotablegbe1pathogenicvariants"><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="gsd4.T.notable_gbe1_pathogenic_variants"><a href="/books/NBK115333/table/gsd4.T.notable_gbe1_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobgsd4Tnotablegbe1pathogenicvariants">Table 5. </a></h4><p class="float-caption no_bottom_margin">Notable <i>GBE1</i> Pathogenic Variants </p></div></div></div></div><div id="gsd4.References"><h2 id="_gsd4_References_">References</h2><div id="gsd4.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.akman.2015.441">Akman HO, Kakhlon O, Coku J, Peverelli L, Rosenmann H. RozensteinTsalkovich L, Turnbull J, Meiner V, Chama L, Lerer I, Shpitzen S, Leitersdorf E, Paradas C, Wallace M, Schiffmann R, Dimauro S, Lossos A, Minassian BA. Deep intronic GBE1 mutation in manifesting heterozygous patients with adult polyglucosan body disease. <span><span class="ref-journal">JAMA Neurol. </span>2015;<span class="ref-vol">72</span>:441–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25665141" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25665141</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.bendrothasmussen.2016.38">Bendroth-Asmussen L, Aksglaede L, Gernow AB, Lund AM. Glycogen storage disease type IV: a case with histopathologic findings in first-trimester placental tissue. <span><span class="ref-journal">Int J Gynecol Pathol. </span>2016;<span class="ref-vol">35</span>:38–40.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26166723" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26166723</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.brown.1983.636">Brown DH, Brown BI. Studies of the residual glycogen branching enzyme activity present in human skin fibroblasts from patients with type IV glycogen storage disease. <span><span class="ref-journal">Biochem Biophys Res Commun. </span>1983;<span class="ref-vol">111</span>:636–43.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/6220706" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6220706</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.burrow.2006.878">Burrow TA, Hopkin RJ, Bove KE, Miles L, Wong BL, Choudhary A, Bali D, Li SC, Chen YT. Non-lethal congenital hypotonia due to glycogen storage disease type IV. <span><span class="ref-journal">Am J Med Genet A. </span>2006;<span class="ref-vol">140</span>:878–82.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16528737" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16528737</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.chen.2001">Chen Y. Glycogen storage disease. In: Scriver CR, Beaudet AS, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B, eds. <em>The Metabolic and Molecular Basis of Inherited Disease</em>. 8 ed. New York, NY: McGraw-Hill; 2001:1521-51.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.choi.2018.365">Choi SY, Kang B, Choe JY, Lee Y, Jang HJ, Park HD, Lee SK, Choe YH. A case of glycogen storage disease IV with rare homozygous mutations in the glycogen branching enzyme gene. <span><span class="ref-journal">Pediatr Gastroenterol Hepatol Nutr. </span>2018;<span class="ref-vol">21</span>:365–8.</span> [<a href="/pmc/articles/PMC6182483/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6182483</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30345254" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30345254</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.chu.2018.849">Chu ML, Moran E. The limb-girdle muscular dystrophies: is treatment on the horizon? <span><span class="ref-journal">Neurotherapeutics. </span>2018;<span class="ref-vol">15</span>:849–62.</span> [<a href="/pmc/articles/PMC6277288/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6277288</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30019308" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30019308</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.dainese.2016.512">Dainese L, Adam N, Boudjemaa S, Hadid K, Rosenblatt J, Jouannic JM, Heron D, Froissart R, Coulomb A. Glycogen storage disease type IV and early implantation defect: early trophoblastic involvement associated with a new GBE1 mutation. <span><span class="ref-journal">Pediatr Dev Pathol. </span>2016;<span class="ref-vol">19</span>:512–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25489661" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25489661</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.davis.2008.137">Davis MK, Weinstein DA. Liver transplantation in children with glycogen storage disease: controversies and evaluation of the risk/benefit of this procedure. <span><span class="ref-journal">Pediatr Transplant. </span>2008;<span class="ref-vol">12</span>:137–45.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18307661" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18307661</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.ewert.1999.850">Ewert R, Gulijew A, Wensel R, Dandel M, Hummel M, Vogel M, Meyer R, Hetzer R. Glycogenosis type IV as a seldom cause of cardiomyopathy - report about a successful heart transplantation. <span><span class="ref-journal">Z Kardiol. </span>1999;<span class="ref-vol">88</span>:850–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10552189" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10552189</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.fernandez.2010.269">Fernandez C, Halbert C, De Paula AM, Lacroze V, Froissart R. FigarellaBranger D, Chabrol B, Pellissier JF. Non-lethal neonatal neuromuscular variant of glycogenosis type IV with novel GBE1 mutations. <span><span class="ref-journal">Muscle Nerve. </span>2010;<span class="ref-vol">41</span>:269–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19813197" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19813197</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.francopalacios.2016.4092">Franco-Palacios MA, Martin MD, Wierenga KJ, Lake JR, Davis AC, Wartchow EP, Mierau GW, Fung KM. Adult polyglucosan body disease with reduced glycogen branching enzyme activity and heterozygous GBE1 mutation mimicking a low-grade glioma. <span><span class="ref-journal">Int J Clin Exp Pathol. </span>2016;<span class="ref-vol">9</span>:4092–100.</span></div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.howell.1991.55">Howell RR. Continuing lessons from glycogen storage diseases. <span><span class="ref-journal">N Engl J Med. </span>1991;<span class="ref-vol">324</span>:55–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1984166" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1984166</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.iijima.2018.31">Iijima H, Iwanoa R, Tanakab Y, Muroyaa K, Fukudac T, Sugied H, Kurosawae K, Adachi M. Analysis of GBE1 mutations via protein expression studies in glycogen storage disease type IV: a report on a non-progressive form with a literature review. <span><span class="ref-journal">Mol Genet Metab Rep. </span>2018;<span class="ref-vol">17</span>:31–7.</span> [<a href="/pmc/articles/PMC6140619/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6140619</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30228975" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30228975</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.klein.2004.323">Klein CJ, Boes CJ, Chapin JE, Lynch CD, Campeau NG, Dyck PJ, Dyck PJ. Adult polyglucosan body disease: case description of an expanding genetic and clinical syndrome. <span><span class="ref-journal">Muscle Nerve. </span>2004;<span class="ref-vol">29</span>:323–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14755501" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14755501</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.li.2010.s83">Li SC, Chen CM, Goldstein JL, Wu JY, Lemyre E, Burrow TA, Kang PB, Chen YT, Bali DS. Glycogen storage disease type IV: novel mutations and molecular characterization of a heterogeneous disorder. <span><span class="ref-journal">J Inherit Metab Dis. </span>2010;<span class="ref-vol">33</span>:S83–90.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20058079" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20058079</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.li.2012.204">Li SC, Hwu WL, Lin JL, Bali DS, Yang C, Chu SM, Chien YH, Chou HC, Chen CY, Hsieh WS, Tsao PN, Chen YT, Lee NC. Association of the congenital neuromuscular form of glycogen storage disease type IV with a large deletion and recurrent frameshift mutation. <span><span class="ref-journal">J Child Neurol. </span>2012;<span class="ref-vol">27</span>:204–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21917543" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21917543</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.lossos.1998.867">Lossos A, Meiner Z, Barash V, Soffer D, Schlesinger I, Abramsky O, Argov Z, Shpitzen S, Meiner V. Adult polyglucosan body disease in Ashkenazi Jewish patients carrying the Tyr329Ser mutation in the glycogen-branching enzyme gene. <span><span class="ref-journal">Ann Neurol. </span>1998;<span class="ref-vol">44</span>:867–72.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9851430" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9851430</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.magoulas.2012.943">Magoulas PL, El-Hattab AW, Roy A, Bali DS, Finegold MJ, Craigen WJ. Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review. <span><span class="ref-journal">Hum Pathol. </span>2012;<span class="ref-vol">43</span>:943–51.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22305237" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22305237</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.mcconkierosell.1996.51">McConkie-Rosell A, Wilson C, Piccoli DA, Boyle J, DeClue T, Kishnani P, Shen JJ, Boney A, Brown B, Chen YT. Clinical and laboratory findings in four patients with the non-progressive hepatic form of type IV glycogen storage disease. <span><span class="ref-journal">J Inherit Metab Dis. </span>1996;<span class="ref-vol">19</span>:51–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8830177" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8830177</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.mochel.2012.433">Mochel F, Schiffmann R, Steenweg ME, Akman HO, Wallace M, Sedel F, Laforêt P, Levy R, Powers JM, Demeret S, Maisonobe T, Froissart R, Da Nobrega BB, Fogel BL, Natowicz MR, Lubetzki C, Durr A, Brice A, Rosenmann H, Barash V, Kakhlon O, Gomori JM, van der Knaap MS, Lossos A. Adult polyglucosan body disease: natural history and key magnetic resonance imaging findings. <span><span class="ref-journal">Ann Neurol. </span>2012;<span class="ref-vol">72</span>:433–41.</span> [<a href="/pmc/articles/PMC4329926/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4329926</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23034915" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23034915</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.moses.2002.177">Moses SW, Parvari R. The variable presentations of glycogen storage disease type IV: a review of clinical, enzymatic and molecular studies. <span><span class="ref-journal">Curr Mol Med. </span>2002;<span class="ref-vol">2</span>:177–88.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11949934" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11949934</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.paradas.2014.41">Paradas C, Akman HO, Ionete C, Lau H, Riskind PN, Jones DE, Smith TW, Hirano M, Dimauro S. Branching enzyme deficiency: expanding the clinical spectrum. <span><span class="ref-journal">JAMA Neurol. </span>2014;<span class="ref-vol">71</span>:41–7.</span> [<a href="/pmc/articles/PMC6148323/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6148323</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24248152" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24248152</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.ravenscroft.2013.165">Ravenscroft G, Thompson EM, Todd EJ, Yau KS, Kresoje N, Sivadorai P, Friend K, Riley K, Manton ND, Blumbergs P, Fietz M, Duff RM, Davis MR, Allcock RJ, Laing NG. Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations. <span><span class="ref-journal">Neuromuscul Disord. </span>2013;<span class="ref-vol">23</span>:165–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23218673" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23218673</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.reusche.1992.36">Reusche E, Aksu F, Goebel HH, Shin YS, Yokota T, Reichmann H. A mild juvenile variant of type IV glycogenosis. <span><span class="ref-journal">Brain Dev. </span>1992;<span class="ref-vol">14</span>:36–43.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1375445" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1375445</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.rosenthal.1995.373">Rosenthal P, Podesta L, Grier R, Said JW, Sher L, Cocjin J, Watanabe F, Vasiliauskas E, van de Velde R, Makowka L. Failure of liver transplantation to diminish cardiac deposits of amylopectin and leukocyte inclusions in type IV glycogen storage disease. <span><span class="ref-journal">Liver Transpl Surg. </span>1995;<span class="ref-vol">1</span>:373–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9346615" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9346615</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.said.2016.152">Said SM, Murphree MI, Mounajjed T, El-Youssef M, Zhang L. A novel GBE1 gene variant in a child with glycogen storage disease type IV. <span><span class="ref-journal">Hum Pathol. </span>2016;<span class="ref-vol">54</span>:152–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27107456" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27107456</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.sampaolo.2015.247">Sampaolo S, Esposito T, Gianfrancesco F, Napolitano F, Lombardi L, Lucà R, Roperto F, Di Iorio G. A novel GBE1 mutation and features of polyglucosan bodies autophagy in adult polyglucosan body disease. <span><span class="ref-journal">Neuromuscul Disord. </span>2015;<span class="ref-vol">25</span>:247–52.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25544507" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25544507</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.schr_der.1993.419">Schröder JM, May R, Shin YS, Sigmund M, Nase-Hüppmeier S. Juvenile hereditary polyglucosan body disease with complete branching enzyme deficiency (type IV glycogenosis). <span><span class="ref-journal">Acta Neuropathol. </span>1993;<span class="ref-vol">85</span>:419–30.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7683169" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7683169</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.sokal.1992.200">Sokal EM, Van Hoof F, Alberti D, de Ville de Goyet J, de Barsy T, Otte JB. Progressive cardiac failure following orthotopic liver transplantation for type IV glycogenosis. <span><span class="ref-journal">Eur J Pediatr. </span>1992;<span class="ref-vol">151</span>:200–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1601012" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1601012</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.tay.2004.253">Tay SK, Akman HO, Chung WK, Pike MG, Muntoni F, Hays AP, Shanske S, Valberg SJ, Mickelson JR, Tanji K, DiMauro S. Fatal infantile neuromuscular presentation of glycogen storage disease type IV. <span><span class="ref-journal">Neuromuscul Disord. </span>2004;<span class="ref-vol">14</span>:253–60.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15019703" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15019703</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.thon.1993.7509">Thon VJ, Khalil M, Cannon JF. Isolation of human glycogen branching enzyme cDNAs by screening complementation in yeast. <span><span class="ref-journal">J Biol Chem. </span>1993;<span class="ref-vol">268</span>:7509–13.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8463281" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8463281</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.troisi.2014.354">Troisi RI, Elsheikh YM, Shagrani MA, Broering D. First fully laparoscopic donor hepatectomy for pediatric liver transplantation using the indocyanine green near-infrared fluorescence imaging in the Middle East: a case report. <span><span class="ref-journal">Ann Saudi Med. </span>2014;<span class="ref-vol">34</span>:354–7.</span> [<a href="/pmc/articles/PMC6152557/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6152557</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25811211" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25811211</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="gsd4.REF.ziemssen.2000.536">Ziemssen F, Sindern E, Schröder JM, Shin YS, Zange J, Kilimann MW, Malin JP, Vorgerd M. Novel missense mutations in the glycogen-branching enzyme gene in adult polyglucosan body disease. <span><span class="ref-journal">Ann Neurol. </span>2000;<span class="ref-vol">47</span>:536–40.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10762170" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10762170</span></a>]</div></p></li></ul></div></div><div id="gsd4.Chapter_Notes"><h2 id="_gsd4_Chapter_Notes_">Chapter Notes</h2><div id="gsd4.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>1 August 2019 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>3 January 2013 (me) Review posted live</div></li><li class="half_rhythm"><div>17 September 2012 (aeh) Original submission</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK115333_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Pilar L Magoulas</span>, MS, CGC<div class="affiliation small">Baylor College of Medicine<br />Texas Children's Hospital<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.mcb@saluogam" class="oemail">ude.mcb@saluogam</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Ayman W El-Hattab</span>, MD, FAAP, FACMG<div class="affiliation small">Associate Professor, Department of Clinical Sciences<br />College of Medicine<br />University of Sharjah<br />Sharjah, United Arab Emirates<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.oohay@wabattahle" class="oemail">moc.oohay@wabattahle</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">January 3, 2013</span>; Last Update: <span itemprop="dateModified">August 1, 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>Magoulas PL, El-Hattab AW. Glycogen Storage Disease Type IV. 2013 Jan 3 [Updated 2019 Aug 1]. 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/gsd3/?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/gsd5/?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="figobgsd4Tmoleculargenetictestingusedin"><div id="gsd4.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Glycogen Storage Disease Type IV</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK115333/table/gsd4.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__gsd4.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_gsd4.T.molecular_genetic_testing_used_in_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_gsd4.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_gsd4.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_gsd4.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GBE1</i>
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</td><td headers="hd_h_gsd4.T.molecular_genetic_testing_used_in_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_gsd4.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">62/84 (74%) <sup>4, 5</sup></td></tr><tr><td headers="hd_h_gsd4.T.molecular_genetic_testing_used_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>6</sup></td><td headers="hd_h_gsd4.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8/84 (10%) <sup>7</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="gsd4.TF.1.1"><p class="no_margin">See <a href="/books/NBK115333/?report=reader#gsd4.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="gsd4.TF.1.2"><p class="no_margin">See <a href="#gsd4.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="gsd4.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="gsd4.TF.1.4"><p class="no_margin">
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<a class="bibr" href="#gsd4.REF.magoulas.2012.943" rid="gsd4.REF.magoulas.2012.943">Magoulas et al [2012]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="gsd4.TF.1.5"><p class="no_margin">Of 42 affected individuals, 37 had at least one identifiable variant detected by sequencing analysis; 28 individuals had biallelic pathogenic variants, and six had one identifiable pathogenic variant, implying that the second causative variant was not identified.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="gsd4.TF.1.6"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include 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>7. </dt><dd><div id="gsd4.TF.1.7"><p class="no_margin">Of the 42 affected individuals, three were homozygous for exon or multiexon deletions and two were compound heterozygous for one exon or multiexon deletion and one sequence variant detectable by sequence analysis [<a class="bibr" href="#gsd4.REF.li.2012.204" rid="gsd4.REF.li.2012.204">Li et al 2012</a>, <a class="bibr" href="#gsd4.REF.magoulas.2012.943" rid="gsd4.REF.magoulas.2012.943">Magoulas et al 2012</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobgsd4Tothergenesofinterestinthedi"><div id="gsd4.T.other_genes_of_interest_in_the_di" class="table"><h3><span class="label">Table 2a. </span></h3><div class="caption"><p>Other Genes of Interest in the Differential Diagnosis of Perinatal and Congenital Neuromuscular Subtypes of GSD IV</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__gsd4.T.other_genes_of_interest_in_the_di_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2" style="text-align:left;vertical-align:middle;">Differential<br />Diagnosis<br />Disorder</th><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Features of Differential Diagnosis Disorder</th></tr><tr><th headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_4" id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/perinatal & congenital neuromuscular subtypes of GSD IV</th><th headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_4" id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from perinatal & congenital neuromuscular subtypes of GSD IV</th></tr></thead><tbody><tr><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SMN1</i>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/sma/?report=reader">Spinal muscular atrophy</a>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>↓ fetal movement</div></li><li class="half_rhythm"><div>Arthrogryposis</div></li><li class="half_rhythm"><div>Severe congenital hypotonia</div></li><li class="half_rhythm"><div>Cardiopulmonary compromise</div></li></ul>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Tongue fasciculations</div></li><li class="half_rhythm"><div>↓ or absent deep tendon reflexes</div></li></ul>
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</td></tr><tr><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GAA</i>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/gsd2/?report=reader">Pompe disease</a>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Profound hypotonia</div></li><li class="half_rhythm"><div>Respiratory distress</div></li></ul>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypertrophic cardiomyopathy rather than dilated cardiomyopathy</td></tr><tr><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>10 genes <sup>1</sup></td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/pbd/?report=reader">Zellweger spectrum disorder</a>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Profound hypotonia</div></li><li class="half_rhythm"><div>Respiratory distress</div></li></ul>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rhizomelic chondrodysplasia punctata & biochemical peroxisomal abnormalities</td></tr><tr><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>40 genes <sup>2</sup></td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/cdg/?report=reader">Congenital disorders of glycosylation</a>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />(XL)</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Liver disease</div></li><li class="half_rhythm"><div>Cardiomyopathy</div></li></ul>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>Stroke-like episodes</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AR = autosomal recessive; GSD = glycogen storage disease; MOI = mode of inheritance; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="gsd4.TF.2a.1"><p class="no_margin">See <a href="/books/n/gene/pbd/?report=reader">Zellweger spectrum disorder</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="gsd4.TF.2a.2"><p class="no_margin">See OMIM Phenotypic Series: <a href="https://omim.org/phenotypicSeries/PS212065" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Congenital disorders of glycosylation, type I</a> and <a href="https://omim.org/phenotypicSeries/PS212066" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Congenital disorders of glycosylation, type II</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobgsd4Tothergenesofinterestinthedi1"><div id="gsd4.T.other_genes_of_interest_in_the_di_1" class="table"><h3><span class="label">Table 2b. </span></h3><div class="caption"><p>Other Genes of Interest in the Differential Diagnosis of the Classic Hepatic Subtype of GSD IV</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__gsd4.T.other_genes_of_interest_in_the_di_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_2" style="text-align:left;vertical-align:middle;">Differential<br />Diagnosis<br />Disorder</th><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Features of Differential Diagnosis Disorder</th></tr><tr><th headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_4" id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/classic hepatic subtype of GSD IV</th><th headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_4" id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from classic hepatic subtype of GSD IV</th></tr></thead><tbody><tr><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>AGL</i>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/gsd3/?report=reader">GSD III</a>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hepatomegaly</div></li><li class="half_rhythm"><div>Liver disease</div></li><li class="half_rhythm"><div>Myopathy</div></li></ul>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hypoglycemia</div></li><li class="half_rhythm"><div>Hyperlipidemia</div></li></ul>
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</td></tr><tr><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DGUOK</i>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/dguok-mtddepl/?report=reader">Deoxyguanosine kinase deficiency</a>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe hypotonia</div></li><li class="half_rhythm"><div>Liver disease</div></li></ul>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Nystagmus</div></li><li class="half_rhythm"><div>Lactic acidosis</div></li><li class="half_rhythm"><div>Developmental regression</div></li></ul>
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</td></tr><tr><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MPV17</i>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/mpv17-mtdep/?report=reader"><i>MPV17</i>-related mtDNA maintenance defect</a>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Liver disease</div></li><li class="half_rhythm"><div>Hepatomegaly</div></li><li class="half_rhythm"><div>Hypotonia</div></li></ul>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Vomiting</div></li><li class="half_rhythm"><div>Diarrhea</div></li><li class="half_rhythm"><div>Failure to thrive</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AR = autosomal recessive; GSD = glycogen storage disease; MOI = mode of inheritance; mtDNA = mitochondrial DNA</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobgsd4Tothergenesofinterestinthedi2"><div id="gsd4.T.other_genes_of_interest_in_the_di_2" class="table"><h3><span class="label">Table 2c. </span></h3><div class="caption"><p>Other Genes of Interest in the Differential Diagnosis of the Childhood Neuromuscular Subtype of GSD IV</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK115333/table/gsd4.T.other_genes_of_interest_in_the_di_2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__gsd4.T.other_genes_of_interest_in_the_di_2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_2" style="text-align:left;vertical-align:middle;">Differential<br />Diagnosis<br />Disorder</th><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Features of Differential Diagnosis Disorder</th></tr><tr><th headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_4" id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/childhood neuromuscular subtype of GSD IV</th><th headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_4" id="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from childhood neuromuscular subtype of GSD IV</th></tr></thead><tbody><tr><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DMD</i>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/dbmd/?report=reader">Duchenne muscular dystrophy</a>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Dilated cardiomyopathy</div></li><li class="half_rhythm"><div>Myopathy</div></li></ul>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Calf pseudohypertrophy</div></li><li class="half_rhythm"><div>Abnormal dystrophin staining on muscle biopsy</div></li></ul>
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</td></tr><tr><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>30 genes <sup>1</sup></td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Limb-girdle muscular dystrophy</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />AD</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Myopathy</div></li><li class="half_rhythm"><div>Cardiomyopathy (in some)</div></li></ul>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Winged scapula</td></tr><tr><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mitochondrial DNA</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/mt-overview/?report=reader">Mitochondrial myopathies</a> (Kearns-Sayre, MERRF)</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mat</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Muscle weakness or exercise intolerance</div></li><li class="half_rhythm"><div>Heart failure</div></li></ul>
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</td><td headers="hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_1_4 hd_h_gsd4.T.other_genes_of_interest_in_the_di_2_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Dementia</div></li><li class="half_rhythm"><div>Movement disorders</div></li><li class="half_rhythm"><div>Stroke-like episodes</div></li><li class="half_rhythm"><div>Deafness</div></li><li class="half_rhythm"><div>Blindness</div></li><li class="half_rhythm"><div>Vomiting</div></li><li class="half_rhythm"><div>Seizures</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; GSD = glycogen storage disease; Mat = maternal; MOI = mode of inheritance; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="gsd4.TF.2c.1"><p class="no_margin">See <a class="bibr" href="#gsd4.REF.chu.2018.849" rid="gsd4.REF.chu.2018.849">Chu & Moran [2018]</a> and OMIM Phenotypic Series: <a href="https://omim.org/phenotypicSeries/PS253600" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Muscular dystrophy, limb-girdle, autosomal recessive</a> and <a href="https://omim.org/phenotypicSeries/PS603511" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Muscular dystrophy, limb-girdle, autosomal dominant</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobgsd4Trecommendedevaluationsfollowing"><div id="gsd4.T.recommended_evaluations_following" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Glycogen Storage Disease Type IV</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK115333/table/gsd4.T.recommended_evaluations_following/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__gsd4.T.recommended_evaluations_following_lrgtbl__"><table><thead><tr><th id="hd_h_gsd4.T.recommended_evaluations_following_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_gsd4.T.recommended_evaluations_following_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_gsd4.T.recommended_evaluations_following_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_gsd4.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hepatic</b>
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</td><td headers="hd_h_gsd4.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Liver function studies incl albumin, transaminases, & coagulation profile</td><td headers="hd_h_gsd4.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_gsd4.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cardiac</b>
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</td><td headers="hd_h_gsd4.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to cardiologist for baseline echocardiogram & electrocardiogram</td><td headers="hd_h_gsd4.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for cardiomyopathy</td></tr><tr><td headers="hd_h_gsd4.T.recommended_evaluations_following_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_gsd4.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurodevelopmental evaluation</td><td headers="hd_h_gsd4.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_gsd4.T.recommended_evaluations_following_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_gsd4.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to neurologist for comprehensive examination & baseline assessment of skeletal muscle involvement</td><td headers="hd_h_gsd4.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To monitor disease progression</td></tr><tr><td headers="hd_h_gsd4.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Other</b>
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</td><td headers="hd_h_gsd4.T.recommended_evaluations_following_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_gsd4.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobgsd4Trecommendedsurveillanceforindi"><div id="gsd4.T.recommended_surveillance_for_indi" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Glycogen Storage Disease Type IV</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK115333/table/gsd4.T.recommended_surveillance_for_indi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__gsd4.T.recommended_surveillance_for_indi_lrgtbl__"><table><thead><tr><th id="hd_h_gsd4.T.recommended_surveillance_for_indi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_gsd4.T.recommended_surveillance_for_indi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_gsd4.T.recommended_surveillance_for_indi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_gsd4.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hepatic</b>
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</td><td headers="hd_h_gsd4.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Liver function tests incl liver transaminases, albumin, & coagulation profile (PT & PTT)</div></li><li class="half_rhythm"><div>Abdominal ultrasound examination</div></li></ul>
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</td><td headers="hd_h_gsd4.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency according to severity</td></tr><tr><td headers="hd_h_gsd4.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cardiac</b>
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</td><td headers="hd_h_gsd4.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram</td><td headers="hd_h_gsd4.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If cardiomyopathy was not seen on echocardiogram at diagnosis, repeat echocardiogram every 3 mos in infancy, every 6 mos in early childhood, & annually thereafter.</td></tr><tr><td headers="hd_h_gsd4.T.recommended_surveillance_for_indi_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_gsd4.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic assessment</td><td headers="hd_h_gsd4.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Frequency according to severity</td></tr><tr><td headers="hd_h_gsd4.T.recommended_surveillance_for_indi_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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</td><td headers="hd_h_gsd4.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nutritional assessment</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobgsd4molgenTA"><div id="gsd4.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Glycogen Storage Disease Type IV: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK115333/table/gsd4.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__gsd4.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_gsd4.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_gsd4.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_gsd4.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_gsd4.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_gsd4.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_gsd4.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_gsd4.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/2632" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>GBE1</i>
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</a>
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</td><td headers="hd_b_gsd4.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=2632" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">3p12<wbr style="display:inline-block"></wbr>​.2</a>
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</td><td headers="hd_b_gsd4.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/Q04446" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">1,4-alpha-glucan-branching enzyme</a>
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</td><td headers="hd_b_gsd4.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://databases.lovd.nl/shared/genes/GBE1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GBE1 database</a>
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</td><td headers="hd_b_gsd4.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=GBE1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GBE1</a>
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</td><td headers="hd_b_gsd4.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=GBE1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GBE1</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="gsd4.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="figobgsd4molgenTB"><div id="gsd4.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Glycogen Storage Disease Type IV (<a href="/omim/232500,607839" 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/NBK115333/table/gsd4.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__gsd4.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/232500" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">232500</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">GLYCOGEN STORAGE DISEASE IV; GSD4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/607839" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">607839</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">GLYCOGEN BRANCHING ENZYME; GBE1</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobgsd4Tnotablegbe1pathogenicvariants"><div id="gsd4.T.notable_gbe1_pathogenic_variants" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Notable <i>GBE1</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK115333/table/gsd4.T.notable_gbe1_pathogenic_variants/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__gsd4.T.notable_gbe1_pathogenic_variants_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide<br />Change</th><th id="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Genotype-Phenotype Correlation <sup>1</sup></th></tr></thead><tbody><tr><td headers="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/nuccore/NM_000158.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000158<wbr style="display:inline-block"></wbr>​.3</a>
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<br />
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<a href="/protein/NP_000149.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000149<wbr style="display:inline-block"></wbr>​.3</a>
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</td><td headers="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.986A>C</td><td headers="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Tyr329Ser</td><td headers="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Non-progressive hepatic, APBD</td></tr><tr><td headers="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1544G>A</td><td headers="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg515His</td><td headers="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">APBD</td></tr><tr><td headers="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1571G>A</td><td headers="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg524Gln</td><td headers="hd_h_gsd4.T.notable_gbe1_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Classic hepatic, non-progressive hepatic, APBD</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">APBD = <a href="/books/n/gene/apbd/?report=reader">adult-onset polyglucosan body disease</a></p></div></dd></dl><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="http://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="gsd4.TF.5.1"><p class="no_margin">
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<a class="bibr" href="#gsd4.REF.li.2012.204" rid="gsd4.REF.li.2012.204">Li et al [2012]</a>
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</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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