A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening
A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening
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DOI：
10.1086/426318
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发表时间：
2004-12-01
影响因子：
9.8
通讯作者：
Matern, D
中科院分区：
文献类型：
--
作者：
Ensenauer, R;Vockley, J;Matern, D
异戊酸血症（IVA）是一种先天性亮氨酸代谢缺陷，可导致显著的发病率和死亡率。由于在许多州和国家实施了通过串联质谱进行的新生儿筛查（NBS），IVA现在可以在症状前诊断。对19名通过NBS检测到病情的受试者的IVD基因进行分子遗传分析，在47%的突变等位基因中鉴定出一种重复突变，932 C-->T（A282 V）。令人惊讶的是，家庭研究发现六个健康的哥哥姐姐具有相同的基因型和IVA的生化证据。我们的研究结果表明，经常发生一种新的轻度和潜在的无症状表型的IVA。这对患者管理和咨询有重要影响。
Isovaleric acidemia (IVA) is an inborn error of leucine metabolism that can cause significant morbidity and mortality. Since the implementation, in many states and countries, of newborn screening (NBS) by tandem mass spectrometry, IVA can now be diagnosed presymptomatically. Molecular genetic analysis of the IVD gene for 19 subjects whose condition was detected through NBS led to the identification of one recurring mutation, 932C-->T (A282V), in 47% of mutant alleles. Surprisingly, family studies identified six healthy older siblings with identical genotype and biochemical evidence of IVA. Our findings indicate the frequent occurrence of a novel mild and potentially asymptomatic phenotype of IVA. This has significant consequences for patient management and counseling.