Thirteen Patients with MAT1A Mutations Detected Through Newborn Screening: 13 Years' Experience
Thirteen Patients with MAT1A Mutations Detected Through Newborn Screening: 13 Years' Experience
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DOI：
10.1007/8904_2013_286
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发表时间：
2014-01-01
期刊：
影响因子：
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通讯作者：
Ficicioglu, C.
中科院分区：
文献类型：
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作者：
Chadwick, S.;Fitzgerald, K.;Ficicioglu, C.
背景：蛋氨酸腺苷转移酶 I/III (MATI/III) 缺乏症是持续性孤立性高蛋氨酸血症的最常见遗传原因。患者和方法：这是对 2000 年 1 月至 2013 年 6 月期间通过新生儿筛查检测到的 62 名蛋氨酸升高的新生儿进行的回顾性数据分析。列出了这些患有与 MATI/III 缺乏症相关的 MAT1A 突变的子集的临床、生化和分子发现。结果： 62 名蛋氨酸升高的新生儿中，12 名被鉴定为典型高胱氨酸尿症； 37 例为误报； 13 人被发现患有孤立的持续性高蛋氨酸血症，但没有高胱氨酸尿症的生化标志物、肝功能检查异常或蛋氨酸升高的其他原因。这 13 个人接受了与 MATI/III 缺陷相关的 MAT1A 基因变化的基因检测。 13 例中的 3 例被发现具有常见的常染色体显性 R264H 突变，1 例被发现是两种新致病性突变的复合杂合子，3 例被发现是先前报道的突变的杂合子，这些突变显示当以纯合子或复合杂合子构型存在时，会导致常染色体隐性遗传 MATI/III 缺陷。其余六名患者具有未知临床意义的变异或新突变。对于大多数人来说，蛋氨酸持续高于正常范围，但随着时间的推移呈下降趋势。这 13 个人中没有一个是从低蛋氨酸饮食开始的，并且都具有适合年龄的生长和发育。结论：这些病例表明，即使 MAT1A 基因发生单一变化的个体也可能通过新生儿筛查发现蛋氨酸升高，这种升高可能会在出生后持续数月，而不会产生任何临床后果。
Background: Methionine adenosyltransferase I/III (MATI/III) deficiency is the most common genetic cause of persistent isolated hypermethioninemia.Patients and Methods: This is a retrospective data analysis of 62 newborns with elevated methionine detected by newborn screening between January 2000 and June 2013. The clinical, biochemical, and molecular findings of a subset of these children with MAT1A mutations associated with MATI/III deficiency are presented.Results: Of the 62 newborns with elevated methionine, 12 were identified as having classical homocystinuria; 37 were false-positives; and 13 were found to have isolated persistent hypermethioninemia in the absence of biochemical markers of homocystinuria, abnormal liver function studies, or other causes of elevated methionine. These 13 individuals underwent genetic testing for changes in the MAT1A gene, associated with MATI/III deficiency. Three of 13 were found to have the common autosomal dominant R264H mutation, one was found to be a compound heterozygote for two novel pathogenic mutations, and three were found to be heterozygotes for previously reported mutations shown to cause autosomal recessive MATI/III deficiency when present in homozygous or a compound heterozygous configuration. The remaining six patients had variants of unknown clinical significance or novel mutations. For the majority of individuals, methionine persisted above the normal range but trended downward over time. None of these 13 individuals was started on a low-methionine diet, and all have age-appropriate growth and development.Conclusion: These cases show that individuals with even single changes in the MAT1A gene may have elevations in methionine identified by newborn screening, which may persist for months after birth without any clinical consequences.