Abstract:

Objective    To analyze the clinical features， mutation types， treatment and outcomes of methylmalonic acidemia combined with homocysteinemia（MMA-HC） in children，in order to improve the clinical understanding of this disease.
Methods    The clinical data，mutation types，treatment and outcomes of 11 children with MMA-HC were retrospectively analyzed to find the relationships of clinical phenotypes and genotypes with the prognosis of the early-onset（≤1 year） and late-onset （＞1 year） patients. Results    In the 9 early-onset children with more serious clinical manifestations，the major gene mutation type was c.609G＞A and C.658_660delAAG；the mutation types of 2 cases of late-onset children were c.482G＞A/c.609 G＞A and c.394C＞T/c.80A＞G compound heterozygous mutations. The children with C.609G＞A/c.658_660delAAG compound heterozygous mutation in early-onset patients had poorer clinical manifestations and prognosis. In contrast，the other early-onset children were relatively good. After treatment，the prognosis of late-onset children were usually good. Conclusion    Combined-type MMA children have various clinical manifestations and individual differences. Seizures，lethargy，feeding difficulty and no increase of weight are the common symptoms in early-onset children，while in late-onset patients there is occult onset，chronic mental disorders，mental retardation and weakness of two legs. Early treatment with hydroxycobalamin can significantly improve the clinical symptoms in the children，but the prognosis still depends on the clinical phenotype and genotype.

Key words: methylmalonic aciduria, homocystinuria, gene mutation, outcome

摘要：

目的    分析甲基丙二酸合并同型半胱氨酸血症（合并型MMA）患儿临床表现、基因突变类型、治疗及预后特点，以提高对该病的临床认识。方法    回顾性分析2012年1月至2015年12月中国医科大学附属盛京医院小儿神经内科门诊及病房收治的11 例合并型MMA患儿的临床表现、 辅助检查、 基因检测结果及治疗效果， 分析早发型（≤ 1 岁）及晚发型（＞1 岁）患儿临床表现及基因突变类型与预后的关系。结果    早发型患儿9例，临床表现较重，主要基因突变类型为c.609G＞A及c.658_660delAAG。晚发型2例， 突变类型分别为c.482G＞A/c.609 G＞A及c.394C＞T/c.80A＞G复合杂合突变。早发型患儿中，3例基因突变类型为c.609G＞A/c.658_660delAAG复合杂合突变的患儿临床表现最重，预后差，余患儿预后相对较好。晚发型患儿经治疗后，预后较好。结论    合并型MMA患儿临床表现多样，个体差异大。早发型患儿常以抽搐、嗜睡、喂养困难及体重不增为主要临床表现，晚发型患儿起病隐匿，呈慢性病程，主要表现为精神异常、智能损害及双下肢运动障碍。早期采用羟钴胺治疗，可明显改善合并型MMA患儿临床症状，但其预后仍与临床表型及基因型有关。

关键词: 甲基丙二酸血症, 同型半胱氨酸血症, 基因突变, 预后