Division of Pediatric Neurology, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Division of Pediatric Genetics, Metabolism, and Genomic Medicine, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Am J Med Genet A. 2023 Jun;191(6):1614-1618. doi: 10.1002/ajmg.a.63176. Epub 2023 Mar 9.
Ethylmalonic encephalopathy (EE) is a rare, severe, autosomal recessive condition caused by pathogenic variants in ETHE1 leading to progressive encephalopathy, hypotonia evolving to dystonia, petechiae, orthostatic acrocyanosis, diarrhea, and elevated ethylmalonic acid in urine. In this case report, we describe a patient with only mild speech and gross motor delays, subtle biochemical abnormalities, and normal brain imaging found to be homozygous for a pathogenic ETHE1 variant (c.586G>A) via whole exome sequencing. This case highlights the clinical heterogeneity of ETHE1 mutations and the utility of whole-exome sequencing in diagnosing mild cases of EE.
乙基丙二酸脑病 (EE) 是一种罕见的、严重的、常染色体隐性疾病，由 ETHE1 中的致病性变异引起，导致进行性脑病、从低张力发展为张力障碍、瘀点、体位性肢端发绀、腹泻和尿液中乙基丙二酸升高。在本病例报告中，我们描述了一名患者，仅表现为轻度言语和粗大运动发育迟缓、细微生化异常，且脑部影像学正常，通过全外显子组测序发现其为致病性 ETHE1 变异（c.586G>A）的纯合子。该病例突出了 ETHE1 突变的临床异质性和全外显子组测序在诊断 EE 轻度病例中的作用。
