MEGDEL syndrome is an autosomal recessive disorder, clinically characterized by 3-methylglutaconic aciduria, psychomotor delay, muscle hypotonia, sensorineural deafness, and Leigh-like lesions on brain magnetic resonance imaging. MEGDEL syndrome is due to mutations in the serine active site-containing protein 1 (SERAC1) gene. The SERAC1 protein is localized at the interface between the mitochondria and the endoplasmic reticulum in the mitochondrion-associated membrane fraction, which is essential for phospholipid exchange. SERAC1 was identified as a key player in phosphatidylglycerol remodeling, which is essential for both mitochondrial function and intracellular cholesterol trafficking. Since the first description of MEGDEL syndrome in 2006, at least 102 patients have been reported. The phenotypic spectrum of MEGDEL syndrome is much broader than so far anticipated. In addition to the brain, ears, and gastrointestinal tract, the eyes, endocrine organs, heart, peripheral nerves, and the skeletal muscle may be affected. Diagnosing MEGDEL syndrome requires a multidisciplinary approach, including genetic confirmation of a SERAC1 mutation. Treatment is supportive, and the outcome is usually poor with early death, except for the juvenile-onset type.

MEGDEL综合征是一种常染色体隐性遗传疾病，临床特征为3-甲基谷氨酸酸尿症，精神运动延迟，肌肉张力低下，感觉神经性耳聋和脑磁共振成像上的Leigh样病变。MEGDEL综合征是由于丝氨酸活性位点蛋白1（SERAC1）基因。SERAC1蛋白位于线粒体相关膜部分的线粒体和内质网之间的界面，这对于磷脂交换至关重要。SERAC1被认为是磷脂酰甘油重塑的关键参与者，磷脂酰甘油重塑对于线粒体功能和细胞内胆固醇运输都是必不可少的。自2006年首次描述MEGDEL综合征以来，已报告至少102例患者。MEGDEL综合征的表型谱比迄今为止预期的要广泛得多。除了大脑，耳朵和胃肠道外，眼睛，内分泌器官，心脏，外周神经和骨骼肌也可能受到影响。诊断MEGDEL综合征需要采取多学科方法，包括对SERAC1进行基因确认突变。治疗是支持性的，除少年发作型外，预后通常较差，早期死亡。