早发型亚甲基四氢叶酸还原酶缺陷症1例临床及基因分析

Clinical and genetic analysis of early onset methylenetetrahydrofolate reductase deficiency in a child

目的探究MTHFR基因突变引起的亚甲基四氢叶酸还原酶缺陷患儿的临床特点、治疗及预后。方法回顾分析1例MTHFR缺陷导致癫痫、脑积水患儿的临床资料和MTHFR基因检测结果,并复习相关文献。结果女性患儿生后第10天出现抽搐、呼吸不规律、喂养困难、肌张力低下,血同型半胱氨酸水平明显升高(147.9μmol/L);基因测序示MTHFR基因存在复合杂合突变(c.1319_c.1320 insTT,c.1262 G>A),其中c.1319_c.1320 insTT以往未见报道。予甜菜碱、亚叶酸钙、维生素B_6、维生素B_(12)治疗2周后,患儿血清总同型半胱氨酸水平下降,临床症状好转,但随后一个月内出现明显脑积水,精神运动发育明显迟缓。结论早发型亚甲基四氢叶酸还原酶缺陷患儿可在生后早期即有表现,血同型半胱氨酸测定及基因检测有助于早期诊断和干预。

Objective To explore the clinical characteristics,treatment and prognosis of methylenetetrahydrofolate reductase deficiency caused by MTHFR gene mutation.Methods The clinical data and MTHFR gene test results in one child with epilepsy and hydrocephalus caused by MTHFR deficiency were retrospectively analyzed,and the related literature were reviewed.Results Convulsions,irregular breathing,feeding difficulties,hypotonia and elevated homocysteine levels(147.9μmol/L)were observed on the 10th day after birth in a female infant.Gene sequencing showed that there were compound heterozygous mutations in MTHFR gene(c.1319_c.1320 insTT and c.1262G>A)and the mutation c.1319_c.1320 insTT was first reported.After 2 weeks of treatment with betaine,calcium folate,vitamin B6 and vitamin B12,the serum total homocysteine level was decreased and the clinical symptoms were improved,but apparent hydrocephalus and mental retardation happened within the next one month.Conclusion Early onset methylenetetrahydrofolate reductase deficiency can be manifested in the early postnatal period.Blood homocysteine determination and gene detection are helpful for early diagnosis and intervention.