1例父源性3-甲基巴豆酰辅酶A羧化酶缺乏症的临床特点及家系分析

Clinical Features and Family Analysis of a Case of Paternal 3-methylcrotonyl Coenzyme A Carboxylase Deficiency

目的报道1例新生儿疾病筛查发现父源性3-甲基巴豆酰辅酶A羧化酶缺乏症(3-Methylcrotonyl-CoA carboxylase deficiency,MCCD)的临床特点、基因诊断及家系分析。方法回顾性分析1例新生儿疾病筛查发现3-羟基异戊酰肉碱(3-hydroxyisovalerylcarnitine,C5OH)增高的新生儿,尿有机酸分析及基因检测证实为父源性MCCD。结果该新生儿初筛血串联质谱C5OH轻度增高,尿有机酸结果正常,其父亲血串联质谱示C5OH明显增高,血浆游离肉碱降低,母亲血串联质谱正常。基因分析结果证实新生儿为MCCC1基因c.980C>G(p.Ser327Ter)杂合变异,其父亲为MCCC1基因c.980C>G(p.Ser327Ter)纯合无义变异。结论新生儿筛查发现持续轻度C5OH水平升高的情况时应考虑父源性MCCD。定期随访仍然是MCCD治疗管理的重心。

Objective To report the clinical characteristics,gene diagnosis and family analysis of a case of paternal 3-methylcrotonyl-CoA carboxylase deficiency(MCCD)found in Newborn screening(NBS).MethodsRetrospective analysis was performed on a newborn who was found to have increased 3-hydroxyisovaleryl carnitine(C5OH)through NBS.Urine organic acid analysis(GC/MS)was carried out on him.His parents performed tandem mass spectrometry(MS/MS).Finally,the clinical diagnosis was confirmed by gene detection.ResultsSlight elevated plasma C5OH concentration was detected via MS/MS by NBS in the newborn,whose urine GC/MS was normal.Evaluation of his parents revealed increased C5OHand low C0 in his father,while normal MS/MS results were achieved from his mother.Sequencing analyses demonstrated that the newborn carries a single mutant methylcrotonyl-CoA carboxylase subunit 1(MCCC1)nonsense allele(c.980C>G)and a homozygous nonsense variation c.980C>G was found in his father.Conclusions Paternal MCCD should be considered in neonates exhibiting a persistent slight increase in C5OH levels.Basic follow-up treatments remain the cornerstone of successfully mitigating the lifelong effects of MCCD.