Novel mutations causing medium chain acyl-CoA dehydrogenase deficiency:: Under-representation of the common c.985 A > G mutation in the New York State population
Novel mutations causing medium chain acyl-CoA dehydrogenase deficiency:: Under-representation of the common c.985 A > G mutation in the New York State population
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DOI：
10.1002/ajmg.a.32192
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发表时间：
2008-03-01
影响因子：
2
通讯作者：
Caggana, Michele
中科院分区：
文献类型：
--
作者：
Nichols, Matthew J.;Saavedra-Matiz, Carlos A.;Caggana, Michele
中链酰基辅酶A脱氢酶缺乏症（MCADD）是最常见的脂肪酸氧化障碍之一。患有MCADD的儿童亚群存在由禁食或疾病引起的代谢危象，变得嗜睡，并且可以经历癫痫发作或昏迷，在首次发作期间达到20%的死亡率。这些代谢危机的频率可以通过早期诊断和治疗来降低。美国MCADD的患病率估计为1/15，000，p.K304E（c.985A > G）占突变等位基因的90%。在开始筛查后的18个月内，纽约州新生儿筛查质谱实验室筛查了385，893名新生儿，并将511份辛酰肉毒碱（C8）水平升高（>= 0.3 μ mol/L）的样本用于分子检测。这些转介，6 p.K304E纯合子和154杂合子被确定。根据儿童儿科医生和/或治疗中心的报告，20名婴儿被生化证实患有MCADD。在这20例中，p.K304E仅占突变等位基因的47.5%。进一步的测试表明，第二个变体p.Y42H占突变等位基因的7.5%，而其余45%是未知的。对所有确诊的非p.K304E纯合子婴儿的样本和C8水平>= 1.0 μ mol/L的样本进行测序（n = 16）。检测到六个新的和七个以前报道的突变。这些结果表明，p.K304 E在患有MCADD的纽约新生儿中的代表性远低于目前的文献估计，其完整的突变谱仍然未知。(C)2008 Wiley-Liss，Inc.
Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is one of the most common fatty acid oxidation disorders. A subpopulation of children with MCADD present with metabolic crisis induced by fasting or illness, become lethargic, and can experience seizures or coma, culminating in a 20% mortality rate during the first episode. The frequency of these metabolic crises can be reduced with early diagnosis and treatment. The prevalence of MCADD in the United States is estimated to be 1 per 15,000 with p.K304E (c.985A > G) accounting for 90% of mutant alleles. In an 18-month period after initiating screening, the New York State Newborn Screening Mass Spectrometry Laboratory screened 385,893 newborns and referred 511 samples with elevated (>= 0.3 mu mol/L) octanoylcarnitine (C8) levels for molecular testing. Of these referrals, six p.K304E homozygotes and 154 heterozygotes were identified. Twenty infants were biochemically confirmed with MCADD, per report from the child's pediatrician and/or treatment center. In these 20 cases, p.K304E accounted for only 47.5% of the mutant alleles. Further testing showed a second variant, p.Y42H, accounted for 7.5% of mutant alleles while the remaining 45% were unknown. Samples from all diagnosed non-p.K304E homozygous infants, and samples with C8 levels >= 1.0 mu mol/L were sequenced (n = 16). Six novel and seven previously reported mutations were detected. These results suggest that p.K304E has a far lower representation in New York newborns with MCADD than current literature estimates and its full mutational spectrum is still unknown. (C) 2008 Wiley-Liss, Inc.