晚发型甲基丙二酸尿症合并同型半胱氨酸血症临床及分子遗传学特点研究

目的分析1例晚发型甲基丙二酸尿症合并同型半胱氨酸血症家系的临床及分子遗传学特点并对相关文献进行复习。方法采用Sanger测序对收集的1例以精神症状为首发症状的该病家系进行MMACHC基因突变的检测并总结分析相关文献。结果测序发现先证者MMACHC基因2号外显子的1个新错义突变(c.160AC)和4号外显子的一个已知错义突变(c.482GA)。通过文献复习提示,在该病中临床症状以认知障碍和精神行为异常最常见,MMACHC基因突变以c.609GA和c.271dup A最常见。结论 MMACHC基因的c.160AC和c.482GA复合杂合突变是本例患者的病因,MMACHC基因在该病具有致病作用;该疾病属于罕见疾病,临床异质性很高,临床上容易漏诊误诊,当出现不明原因的精神行为异常时宜考虑该诊断。

Clinical and molecular genetic features of late-onset methylmalonic aciduria with homocystinemia

Objective To investigate the clinical and molecular genetic features of a family with late-onset methylmalonic aciduria and homocystinemia,and to review related articles.Methods Sanger sequencing was performed for one family with mental symptoms as initial symptoms to detect MMACHC gene mutations,and related articles were summarized and analyzed.Results A novel missense mutation,c.160A ＞ C,in exon 2,and a previously reported missense mutation,c.482G ＞ A,in exon 4 of MMACHC gene were detected in the proband.Literature review found that cognitive impairment and mental and behavioral disorders were the most common symptoms in patients with this disease,and the most common mutations of MMACHC gene were c.609G ＞ A and c.271dupA.Conclusions The compound heterozygote mutations of c.160A ＞ C and c.482G ＞ A in MMACHC gene are the cause of late-onset methylmalonic aciduria with homocystinemia in this patient,suggesting that MMACHC gene may have a pathogenic effect in this disease.This disease is rare and has high clinical heterogeneity,which may lead to missed diagnosis and misdiagnosis.This disease should be considered in case of unexplained mental and behavioral disorders.