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

MEGDHEL 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.