Abstract: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency（HMGCLD），also known as 3-hydroxy-3-methylglutaric aciduria，is a rare autosomal recessive disorder. The disease can present at any age，most often triggered by stress factors such as infection，hunger，or fatigue，which can lead to acute metabolic decompensation. Without timely intervention，the disease may be fatal，while survivors often develop neurological sequelae. Approximately one-third of reported cases have first onsets during the neonatal period. Common clinical manifestations include hypoketotic hypoglycemia，hyperammonemia，severe metabolic acidosis，hepatic dysfunction，seizures，and coma. Diagnosis relies on plasma amino acid and acylcarnitine profiling，urinary organic acid analysis，and genetic testing. Biochemically，patients typically show elevated 3-hydroxyisovalerylcarnitine（C5OH） and reduced free carnitine in plasma，increased urinary excretion of 3-hydroxy-3-methylglutaric acid and 3-methylglutaconic acid，and HMGCL gene variants. HMGCLD is a treatable organic acidemia. Long-term management focuses on restricting protein and fat intake and supplementation of L-carnitine and other essential nutrients. To enhance clinical awareness of the disease，this review provides a comprehensive summary of the pathogenesis，clinical manifestations，diagnostic approaches，and therapeutic strategies for HMGCLD.

Key words: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, 3-hydroxy-3-methylglutaric aciduria, inherited metabolic diseases, organic aciduria

摘要： 3-羟基-3-甲基戊二酸辅酶A裂解酶（3-hydroxy-3-methylglutaryl-CoA lyase，HMGCL）缺乏症又称3-羟基-3-甲基戊二酸尿症，是一种罕见病，为常染色体隐性遗传病，患者可能在任何年龄发病，多因感染、饥饿、疲劳等应激诱发急性发作，导致急性代谢危象，如不及时救治，可能猝死，一些存活者遗留神经系统后遗症。已报道的病例中1/3在新生儿期起病，常见临床表现为低酮性低血糖、高氨血症、严重代谢性酸中毒、肝功能损害、抽搐、昏迷等。血氨基酸及酰基肉碱谱、尿有机酸分析及基因检测是诊断该病的关键，患儿血羟异戊酰肉碱增高，游离肉碱降低，尿3-羟基-3-甲基戊二酸、3-甲基戊烯二酸增高，HMGCL基因变异。该病为可治疗的有机酸尿症，需限制蛋白质、脂肪的摄入，补充左旋肉碱等营养素。为提高对该病的认识，文章对HMGCL缺乏症的发病机制、临床表现、诊断以及治疗等进行全面综述。

关键词: 3-羟基-3-甲基戊二酰辅酶A裂解酶缺乏症, 3-羟基-3-甲基戊二酸尿症, 遗传代谢病, 有机酸尿症