Abduljalil Razan, Ben Turkia Hadhami, Fakhroo Aysha, Skrypnyk Cristina
Department of Pediatrics, King Hamad University Hospital, Manama, Bahrain.
Department of Molecular Medicine, Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Bahrain.
Case Reports Hepatol. 2023 Jun 20;2023:4514552. doi: 10.1155/2023/4514552. eCollection 2023.
Mitochondrial depletion syndromes are well established causes of liver failure in infants. Hepatocerebral variant related to MPV17 gene defect is characterized by infantile onset of progressive liver failure, developmental delay, neurological manifestations, lactic acidosis, hypoglycemia, and mtDNA depletion in liver tissue. We report a hepatocerebral variant of mitochondrial DNA depletion syndrome in a neonate who presented with septic shock picture, hypoglycemia, jaundice, hypotonia, and rotatory nystagmus. Family history was significant for consanguinity and a brother who died at the age of 4 months. Investigations showed mild liver function derangement contrasting with severe coagulopathy, hyperlactatemia, and generalized aminoaciduria. The brain MRI was normal. Next generation sequencing (NGS) panel identified a MPV17 gene missense homozygous pathogenic variant. The infant expired at the age of 2 weeks with refractory ascites. This case illustrates a challenging diagnosis causing liver failure and death in neonatal period. Genetic testing of mitochondrial DNA depletion syndromes should be a part of liver failure workup in addition to other treatable disorders presenting with encephalo-hepatopathy in infancy.
线粒体耗竭综合征是婴儿肝衰竭的公认病因。与MPV17基因缺陷相关的肝脑型变异型的特征为婴儿期起病的进行性肝衰竭、发育迟缓、神经表现、乳酸性酸中毒、低血糖以及肝组织中的线粒体DNA耗竭。我们报告了1例线粒体DNA耗竭综合征的肝脑型变异型新生儿病例，该患儿表现为脓毒症休克、低血糖、黄疸、肌张力减退和旋转性眼球震颤。家族史显示存在近亲结婚情况，且有1名4个月大时死亡的兄弟。检查显示肝功能轻度紊乱，与严重凝血障碍、高乳酸血症和全身性氨基酸尿形成对比。脑部MRI正常。二代测序（NGS）检测板鉴定出1个MPV17基因错义纯合致病性变异。该婴儿在2周龄时因难治性腹水死亡。本病例说明了一种具有挑战性的诊断，可导致新生儿期肝衰竭和死亡。除了婴儿期出现脑肝病的其他可治疗疾病外，线粒体DNA耗竭综合征的基因检测应作为肝衰竭检查的一部分。
