The clinical manifestations, biochemical and metabolic data, genetic variations and treatment data of children with MTHFR gene variant induced hyperhomocysteinemia admitted to Hangzhou Children's Hospital and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2015 to September 2021 were analysed retrospectively. A total of 15 pediatric patients were included, including 10 males and 5 females, with onset ages ranging from 6 days to 18 years old and confirmed ages ranging from 40 days to 18 years old. One confirmed case was detected through neonatal screening, and the remaining 14 cases were all diagnosed through genetic diagnosis after onset. The main clinical manifestations were feeding difficulties, hypotonia, epilepsy, developmental delay. All patients had elevated levels of blood homocysteine, with blood homocysteine levels before and after treatment being (151.46±57.44) μmol/L and (69.96±32.88) μmol/L, significantly decreased after treatment compared with before treatment, with a statistically significant difference (P<0.001). The blood methionine level before the treatment was 9.40 (6.20, 11.96) μmol/L, normal or slightly decreased compared to the reference range. The methionine level returned to normal after treatment. A total of 19 MTHFR gene variants were detected, with 6 being unreported variants and 13 being known variants. c.1316C>T (p.L439P) was the most common variant(16.6%,5/30). All the patients had varied neurological damages, with 7 patients improved after metabolic therapy by carnitine and folinic acid, 8 patients experiencing developmental delay, and 1 patient experiencing frequent epilepsy. The clinical manifestations of MTHFR gene variation-related hyperhomocysteinemia are complex and variable. Early-onset and homozygous variants often have a poor prognosis. Blood homocysteine, blood amino acid analysis, serum total homocysteine assay and gene testing are helpful for early diagnosis.
回顾性分析2015年11月至2021年9月就诊于杭州市儿童医院及上海交通大学医学院附属新华医院的MTHFR基因变异致高同型半胱氨酸血症患儿的主要临床表现、生化代谢指标、基因变异及治疗等资料。共纳入15例患儿，其中男10例，女5例，起病年龄6 d~18岁，确诊年龄40 d~18岁。新生儿筛查确诊病例1例，余14例均为发病后基因诊断。主要表现为喂养困难、肌张力减退、癫痫、发育迟缓。所有患儿血同型半胱氨酸水平均升高，治疗前后血同型半胱氨酸分别为（151.46±57.44）μmol/L及（69.96±32.88）μmol/L，治疗后较治疗前显著下降，差异有统计学意义（P<0.001）。治疗前血蛋氨酸水平为9.40（6.20，11.96）μmol/L，较参考范围正常或略下降，治疗后蛋氨酸均恢复至正常。共检出MTHFR基因变异19种，6种为未报道变异、13种为已知变异。其中最常见变异为c.1316C>T（p.L439P）（16.6%，5/30）。所有患儿存在不同程度的神经系统损害，7例经甜菜碱及亚叶酸等代谢干预治疗后好转，8例出现发育落后，1例仍癫痫发作频繁。MTHFR基因变异致高同型半胱氨酸血症患儿临床表现异质性大，早发型及基因纯合变异多预后不良，血同型半胱氨酸、血氨基酸和基因检测有助于早期诊断。.