3-羟基-3-甲基戊二酰辅酶A裂解酶缺乏症2例患儿的临床及遗传学分析

Clinical and genetic analysis of two children with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency

目的探讨3-羟基-3-甲基戊二酰辅酶A裂解酶缺乏症(HMGCLD)患儿的临床特征和基因变异。方法选择分别于2019年12月和2022年6月在河南省儿童医院确诊的2例HMGCLD患儿作为研究对象。收集患儿的临床资料、实验室检查以及基因检测结果,分析其临床和遗传学特点。结果患儿均表现为反复抽搐、严重低血糖、代谢性酸中毒、肝功能异常等,血氨基酸及酰基肉碱谱中3-羟基-异戊酰肉碱(C5OH)、3-羟基-异戊酰肉碱/辛酰肉碱比值(C5OH/C8)升高,尿有机酸分析3-羟基-3-甲基戊二酸、3-甲基戊二酸、3-甲基戊烯二酸、3-羟基异戊酸及3-甲基巴豆酰甘氨酸增多。患儿1携带HMGCL基因c.722C>T纯合变异,评级为临床意义未明变异(PM2Supporting+PP3)。患儿2携带HMGCL基因c.121C>T纯合变异,评级为致病性变异(PVS1+PM2Supporting+PP4)。结论HMGCLD的急性发作期多表现为低血糖、代谢性酸中毒等代谢紊乱,尿中升高的有机酸有助于鉴别诊断,但确诊有赖于基因检测。

Objective To explore the clinical characteristics and genetic variants of two children with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency(HMGCLD).Methods Two children with HMGCLD diagnosed at Henan Provincial Children′s Hospital respectively in December 2019 and June 2022 were selected as the study subjects.Clinical data and results of laboratory testing were analyzed retrospectively.Results Both children had manifested with repeated convulsions,severe hypoglycemia,metabolic acidosis and liver dysfunction.Blood amino acids and acylcarnitine analysis showed increased 3-hydroxy-isovalyl carnitine(C5OH)and 3-hydroxy-isovalyl carnitine/capryloyl carnitine ratio(C5OH/C8),and urinary organic acid analysis showed increased 3-hydroxyl-3-methyl glutaric acid,3-methyl glutaric acid,3-methyl glutacoic acid,3-hydroxyisoglycine and 3-methylprotarylglycine.Child 1 was found to harbor homozygous c.722C>T variants of the HMGCL gene,which was rated as uncertain significance(PM2_Supporting+PP3).Child 2 was found to harbor homozygous c.121C>T variants of the HMGCL gene,which was rated as pathogenic(PVS1+PM2_Supporting+PP4).Conclusion Acute episode of HMGCLD is usually characterized by metabolic disorders such as hypoglycemia and metabolic acidosis,and elevated organic acids in urine may can facilitate the differential diagnosis,though definite diagnosis will rely on genetic testing.