{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T06:19:00Z","timestamp":1770445140106,"version":"3.49.0"},"reference-count":13,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2025,7,24]]},"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>Glycogen storage disease (GSD) type IV is an autosomal recessive disorder due to a deficiency of glycogen branching enzyme (GBE), leading to accumulation of polyglucosan inclusion in tissues. The congenital neuromuscular variant is a severe subtype presenting as hypotonia, respiratory distress and dilated cardiomyopathy, resulting in early death. Cardiac manifestations as a primary presentation are uncommon in this subtype.<\/jats:p>\n                  <jats:p>\n                    We report the case of a male preterm infant who presented with heart failure attributed initially solely to hypertrophic cardiomyopathy. Genetic testing identified compound heterozygous\n                    <jats:italic>GBE1<\/jats:italic>\n                    variants. Enzymatic testing demonstrated reduced GBE activity, and histopathological findings showed myocardial Periodic acid-Schiff-positive and diastase-resistant inclusions, confirming the diagnosis. Neurological symptoms developed later, increasing the suspicion of a metabolic disorder.\n                  <\/jats:p>\n                  <jats:p>This case represents a unique presentation of this variant of GSD IV, primarily manifesting with hypertrophic cardiomyopathy. It underscores the importance of considering metabolic disorders in infants with cardiomyopathy, even when neurological symptoms are initially absent.<\/jats:p>","DOI":"10.1136\/bcr-2025-266228","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T04:10:22Z","timestamp":1755144622000},"page":"e266228","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Congenital neuromuscular variant of glycogen storage disease type IV presenting as hypertrophic cardiomyopathy"],"prefix":"10.1136","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9282-8435","authenticated-orcid":false,"given":"Genevieve Villablanca","family":"Llanora","sequence":"first","affiliation":[{"name":"Department of Neonatology, KK Women's and Children\u2019s Hospital, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7704-1917","authenticated-orcid":false,"given":"Sylvia Pei Rong","family":"Kam","sequence":"additional","affiliation":[{"name":"Division of Genetics Service, Department of Paediatrics, KK Women's and Children\u2019s Hospital, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth Tou En","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, KK Women's and Children\u2019s Hospital, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shrenik Vora","family":"Jitendrakumar","sequence":"additional","affiliation":[{"name":"Department of Neonatology, KK Women's and Children\u2019s Hospital, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"2025081321101484000_18.8.e266228.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2023.107525"},{"key":"2025081321101484000_18.8.e266228.2","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.177722","article-title":"Natural history study of hepatic glycogen storage disease type IV and comparison to Gbe1ys\/ys model","volume":"9","author":"Koch","year":"2024","journal-title":"JCI Insight"},{"key":"2025081321101484000_18.8.e266228.3","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/jimd.12692","article-title":"Severe neuromuscular forms of glycogen storage disease type IV: Histological, clinical, biochemical, and molecular findings in a large French case series","volume":"47","author":"Lef\u00e8vre","year":"2024","journal-title":"J Inherit Metab Dis"},{"key":"2025081321101484000_18.8.e266228.4","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807309248"},{"key":"2025081321101484000_18.8.e266228.5","unstructured":"Magoulas PL , El-Hattab AW . Glycogen storage disease type IV. In: Adam MP , Feldman J , Mirzaa GM , et al ., eds. GeneReviews. Seattle (WA): University of Washington, 1993."},{"key":"2025081321101484000_18.8.e266228.6","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2022.992406","article-title":"A novel approach to characterize phenotypic variation in GSD IV: Reconceptualizing the clinical continuum","volume":"13","author":"Kiely","year":"2022","journal-title":"Front Genet"},{"key":"2025081321101484000_18.8.e266228.7","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1212\/01.WNL.0000138429.11433.0D","article-title":"Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV)","volume":"63","author":"Bruno","year":"2004","journal-title":"Neurology (ECronicon)"},{"key":"2025081321101484000_18.8.e266228.8","doi-asserted-by":"crossref","first-page":"237","DOI":"10.5114\/aoms.2018.72246","article-title":"Variable clinical presentation of glycogen storage disease type IV: from severe hepatosplenomegaly to cardiac insufficiency. Some discrepancies in genetic and biochemical abnormalities","volume":"14","author":"Szyma\u0144ska","year":"2018","journal-title":"Arch Med Sci"},{"key":"2025081321101484000_18.8.e266228.9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118517"},{"key":"2025081321101484000_18.8.e266228.10","doi-asserted-by":"crossref","DOI":"10.1136\/bcr-2019-230068","article-title":"Glycogen storage disease type IV: dilated cardiomyopathy as the isolated initial presentation in an adult patient","volume":"12","author":"Ndugga-Kabuye","year":"2019","journal-title":"BMJ Case Rep"},{"key":"2025081321101484000_18.8.e266228.11","doi-asserted-by":"crossref","first-page":"616392","DOI":"10.3389\/fgene.2021.616392","article-title":"Value of Exome Sequencing in Diagnosis and Management of Recurrent Non-immune Hydrops Fetalis: A Retrospective Analysis","volume":"12","author":"Zhou","year":"2021","journal-title":"Front Genet"},{"key":"2025081321101484000_18.8.e266228.12","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/764286","article-title":"Cardiac Involvement in Glycogen Storage Disease Type IV: Two Cases and the Two Ends of a Spectrum","volume":"2012","author":"Aksu","year":"2012","journal-title":"Case Rep Med"},{"key":"2025081321101484000_18.8.e266228.13","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines11020363","article-title":"A Broad Characterization of Glycogen Storage Disease IV Patients: A Clinical, Genetic, and Histopathological Study","volume":"11","author":"Wilke","year":"2023","journal-title":"Biomedicines"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2025-266228","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T04:10:24Z","timestamp":1755144624000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2025-266228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":13,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,13]]},"published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1136\/bcr-2025-266228"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2025-266228","relation":{},"ISSN":["1757-790X"],"issn-type":[{"value":"1757-790X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]}}}