单纯性甲基丙二酸血症一例及家系MUT基因突变分析

摘要

目的 探讨甲基丙二酸血症(methylmalonic acidemia,MMA)家系MUT基因的临床特点.方法 对诊治的1例单纯性MMA的临床资料及家系MUT基因突变情况进行回顾性分析.结果 男,52 d.系第3胎第3产,其母孕期体健,父母非近亲结婚,第1胎为足月顺产女婴,出生7d后去世,当时考虑酸中毒,未行遗传代谢病检查;第2胎亦为足月顺产女婴,体健.本例于生后36 d出现抽搐,症状持续10 min缓解,就诊当地医院,入院时呈昏迷状态,伴严重代谢性酸中毒,请我院新生儿科会诊,高度怀疑遗传代谢疾病,急诊采血留尿行遗传代谢病筛查,同时予维生素B12、左卡尼汀等治疗.遗传代谢病筛查结果支持MMA诊断,遂继续上述治疗,后病情平稳出院.出院后患儿父母擅自停药并停用特殊奶粉,20 d后再次昏迷,家属放弃治疗,数日后死亡.通过对患儿及其父母、姐姐进行相关基因高通量测序,发现患儿父亲MUT基因发生了错义突变(c.1106G>A),母亲发生了杂合突变(c.729730insTT).结论 基因测序有助于明确MMA的临床分型,为产前诊断奠定基础,避免缺陷患儿出生.%Objective To investigate clinical characteristics of methylmalonic acidemia ( MMA ) parentage MUT gene. Methods Clinical data of 1 patient with simple MMA and condition of parentage MUT gene mutation was retrospective-ly analyzed. Results A male neonate with 52 d old was the third child by the third births, and his parents were not consan-guineous marriage. The first child was a full-term delivery girl, and she died the 7th d after birth, acidosis was suspected at that time without tests for genetic and metabolic diseases. The second child was also a full-term delivery girl with healthy. The third child had convulsion at the postnatal 36th d, and the symptom was relieved after continue 10 minutes. He visited in local hospital, and he was in comatose state when he had been admitted with severe metabolic acidosis, and the consultation with our hospital was required. Genetic metabolic disease was highly suspected, and screening for genetic metabolic diseases was performed by drawing blood and remaining urine in emergency department, and treatments such as vitamin B12 and Levocarni-tine were given simultaneously. Screening result for genetic metabolic diseases supported the diagnosis of MMA, and the above treatments were continued, and then the neonate was discharged after having stable condition. After discharging, the parents stopped using the drug and special milk powder without doctors's authorization, and the neonate had coma again at the 20th d after discharging, and the family members gave up treatment, and then the neonate died a few days later. Related gene high-throughput sequencing was performed for the neonate and the neonatal parents and sister, and then the missense mutation (c. 1106G>A) was detected in the neonatal father;heterozygosis mutation (c. 729730insTT) was detected in the neonatal mother. Conclusion Gene sequencing helps to confirm clinical MMA classification, and it gives prepare for prenatal diagno-sis to avoid defects in children born.