Objective To investigate the clinical and molecular genetic characteristics of hypermethioninemia caused by methionine adenosyltransferase deficiency. Methods The clinical data and related gene analysis of hypermethioninemia caused by methionine adenosyltransferase deficiency in 3 children were retrospectively analyzed. The core pedigree analysis was carried out. Results Three children (2 boys and 1 girl) aged from 5 months to 3 years, were from 3 unrelated families. All of them had no family history. One case was found in neonatal screening. One case was onset with pathological jaundice at 1 month old. Another case was found due to tremor and growth retardation at 2 years old. Blood amino acid ester acyl carnitine spectrum analysis showed that all of them had significantly elevated levels of methionine at 134.50-790.67 μmol/L. All children had MAT1A mutation in methionine adenosyltransferase gene. One case was heterozygous mutations with third exon c.274T>C and seventh exon c.895C>T mutation; one case had sixth exon c.757G>A homozygous mutation; and another case had seventh exon c.791G>A homozygous mutation. The core pedigree analysis showed that the mutations were from theirs parents respectively. Conclusions For children with neurologic impairment, methionine metabolic disorders should be considered. Blood amino acids and gene analysis are important methods for confirmation of the diagnosis. Neonatal screening is an effective way to detect this disease.%目的 探讨甲硫氨酸腺苷转移酶缺陷导致的高甲硫氨酸血症患儿的临床表现和分子遗传学特点.方法 回顾分析3例因甲硫氨酸腺苷转移酶缺陷导致的高甲硫氨酸血症患儿的临床资料及相关基因分析,并进行核心家系分析.结果 3例患儿,男孩2例,女孩1例,年龄5个月～3岁,来自3个不相关的家系;均无阳性家族史.1例在新生儿筛查时被发现,1例于1个月时病理性黄疸发病,另1例于2岁时因手抖和生长发育落后而就诊.血氨基酸酯酰肉碱谱分析均显示甲硫氨酸显著增高,134.50～790.67μmol/L.患儿均为甲硫氨酸腺苷转移酶编码基因MAT1A突变;1例为复合杂合突变,第3外显子c.274T>C和第7外显子c.895C>T突变;1例为第6外显子c.757G>A纯合突变;另1例为第7外显子c.791G>A纯合突变.核心家系分析示患儿的突变均分别来自父母.结论 对于以神经系统损害为主要表现的患儿应考虑到甲硫氨酸代谢障碍性疾病,血氨基酸和基因分析是明确诊断的重要方法.新生儿筛查是发现此病的有效方法.
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