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Atypical MEGDHEL Syndrome: A Milder Phenotype With Hepatic Presentation and Failure to Thrive Associated With a Homozygous Nonsense Variant of SERAC1

2025-05-12Artigo científico Acesso aberto
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dc.contributor.authorMarchante Pita, Rita
dc.contributor.authorAmaral, Raquel
dc.contributor.authorVilarinho, Laura
dc.contributor.authorDiogo, Luísa
dc.contributor.authorGonçalves, Isabel
dc.contributor.authorNobre, Susana
dc.date.accessioned2026-02-16T13:17:24Z
dc.date.available2026-02-16T13:17:24Z
dc.date.issued2025-05-12
dc.description.abstractMEGDHEL syndrome, caused by a gene defect, is clinically defined as the association of 3-MGA-uria (MEG), deafness (D), hepatopathy (H), encephalopathy (E), and Leigh-like features (L). Clinical presentation typically begins in the neonatal period, with neurological symptoms becoming more evident by 2 years of age. Severe liver involvement has also been reported. We report the case of a 3-year-old boy with increased transaminases and failure to thrive of unknown cause. He was born prematurely at 35 weeks and needed neonatal intensive care support for 24 h due to transient tachypnea. At 18 months, laboratory investigations for failure to thrive revealed elevated transaminases without cholestasis, which persisted on subsequent evaluations. Abdominal wall collateral veins were found during physical examination, and the liver ultrasound revealed steatosis, prompting the decision to proceed with a liver biopsy. Common causes of chronic liver disease were ruled out. Following liver biopsy, performed under general anesthesia, he had an episode of unexplained decompensation (metabolic acidosis, hyperlactatemia, and 3-methylglutaconic aciduria). The aciduria persisted upon subsequent evaluation. Liver histology showed macro/microvesicular steatosis (25%), portal tract inflammation, and mild fibrosis. Cardiac evaluation, along with brain magnetic resonance imaging and spectroscopy, was normal. Further investigations revealed decreased hepatic activity of respiratory mitochondrial chain complexes and marginal mtDNA depletion (28.1%). Analysis of the gene showed homozygosity for p.Y259* (c.777T>G, exon 9). This case report raises awareness for an atypical presentation of MEGDHEL syndrome associated with a homozygous nonsense variant of SERAC1 clinically characterized by mild hypertransaminasemia, failure to thrive, no neurological involvement, and starting in early childhood rather than infancy.eng
dc.description.abstractSummary: -MEGDHEL syndrome is a rare autosomal recessive disorder due to variants in the SERAC1 gene. -MEGDHEL syndrome is characterized by 3-methylglutaconic aciduria (MEG), deafness (D), hepatopathy (H), encephalopathy (E) and Leigh-like features (L). -We report an atypical presentation of MEGDHEL syndrome characterized by mild hepatopathy and failure to thrive, without neurological involvement, associated with a homozygous nonsense SERAC1 variant, expanding the clinical spectrum of the syndrome.eng
dc.identifier.citationJIMD Rep. 2025 May 12;66(3):e70017. doi: 10.1002/jmd2.70017. eCollection 2025 May
dc.identifier.doi10.1002/jmd2.70017
dc.identifier.eissn2192-8312
dc.identifier.pmid40365324
dc.identifier.urihttp://hdl.handle.net/10400.18/10945
dc.language.isoeng
dc.peerreviewedyes
dc.publisherWiley
dc.relation.hasversionhttps://onlinelibrary.wiley.com/doi/10.1002/jmd2.70017
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject3‐Methylglutaconic Aciduria
dc.subjectMEGDEL Syndrome
dc.subjectSERAC1 Gene
dc.subjectHepatopathy
dc.subjectPediatrics
dc.subjectDoenças Genéticas
dc.titleAtypical MEGDHEL Syndrome: A Milder Phenotype With Hepatic Presentation and Failure to Thrive Associated With a Homozygous Nonsense Variant of SERAC1eng
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue3
oaire.citation.startPagee70017
oaire.citation.titleJIMD Reports
oaire.citation.volume66
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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