Marchante Pita Rita, Amaral Raquel, Vilarinho Laura, Diogo Luísa, Gonçalves Isabel, Nobre Susana
Department of Pediatrics, Unidade Local de Saúde de Coimbra Portugal.
Department of Pediatrics Hospital Divino Espírito Santo, Ponta Delgada Azores Portugal.
JIMD Rep. 2025 May 12;66(3):e70017. doi: 10.1002/jmd2.70017. eCollection 2025 May.
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.
MEGDHEL综合征由基因缺陷引起，临床定义为3 -甲基戊二酸尿症（MEG）、耳聋（D）、肝病（H）、脑病（E）和类 Leigh 特征（L）的关联。临床表现通常始于新生儿期，2岁时神经症状变得更加明显。也有严重肝脏受累的报道。我们报告了一例3岁男孩，其转氨酶升高且不明原因发育不良。他在35周时早产，因短暂性呼吸急促需要新生儿重症监护支持24小时。18个月时，针对发育不良的实验室检查显示转氨酶升高但无胆汁淤积，后续评估中仍持续存在。体格检查发现腹壁侧支静脉，肝脏超声显示脂肪变性，促使决定进行肝活检。排除了慢性肝病的常见原因。在全身麻醉下进行肝活检后，他出现了一次不明原因的失代偿（代谢性酸中毒、高乳酸血症和3 -甲基戊二酸尿症）。后续评估时酸尿症持续存在。肝脏组织学显示大/小泡性脂肪变性（25%）、门管区炎症和轻度纤维化。心脏评估以及脑磁共振成像和波谱分析均正常。进一步检查显示呼吸线粒体链复合物的肝脏活性降低以及边缘性线粒体DNA耗竭（28.1%）。基因分析显示p.Y259*（c.777T>G，外显子9）纯合。本病例报告提高了对MEGDHEL综合征非典型表现的认识，该综合征与SERAC1的纯合无义变异相关，临床特征为轻度转氨酶升高、发育不良、无神经受累且始于幼儿期而非婴儿期。
