Ethnicity of children with homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency: findings from screening approximately 1.1 million newborn infants
Ethnicity of children with homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency: findings from screening approximately 1.1 million newborn infants
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DOI：
10.1258/jms.2008.008043
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发表时间：
2008-01-01
影响因子：
2.9
通讯作者：
Dezateux, C.
中科院分区：
文献类型：
--
作者：
Khalid, J. M.;Oerton, J.;Dezateux, C.
目的纯合型c.985A>G中链酰基辅酶A脱氢酶缺乏症（MCADD）是一种起源于白色人种的疾病，但其种族分布尚不清楚。我们估计种族特异性纯合子c.985A>G MCADD出生患病率从一个大规模的英国新生儿screeningstudy.Methods纯合子c.985A>G MCADD病例被确定在6个英语新生儿筛查中心之间的2004年3月1日和2007年2月28日通过筛选约110万新生儿使用串联质谱分析univatised血斑样本定量octancylcarnitine（C8）.对病例的随访生化和突变分析（平均一式三份C8值>= 0.5 μ mol/L）进行审查，以确认诊断。种族确定从临床医生的报告和2001年英国人口普查估计的种族群体的儿童小于1 year.Results六十四名婴儿c.985A>G MCADD纯合子（总患病率5.8每10万活产婴儿; 95%CI 4.4-7.2）。60例（93%）为白色，2例（3%）为混血/其他，2例种族来源不明。未发现亚洲人或黑人纯合子。估计了筛查区域中白色、混血/其他、亚洲和黑人出生的比例，得出白色人群中纯合子c.985 A>G MCADD出生患病率为6.9/100，000（95% CI 5.2-8.8），亚洲人群中95% CI估计值为0-2.7/100，000，黑人人群中为0-5.8。在Hardy-Weinberg条件下，白色人群中c.985 A>G基因携带频率为1/65（95%CI 1/74，1/61）。这与早期发表的观察结果一致，表明由于c.985 A>G突变导致的MCADD是一种白色种族起源的疾病。
Objectives It has been suggested that homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disease of White ethnic origin but little is known regarding its ethnic distribution. We estimated ethnic-specific homozygous c.985A>G MCADD birth prevalence from a large-scale UK newborn screening study.Methods Homozygous c.985A>G MCADD cases were ascertained in six English newborn screening centres between 1 March 2004 and 28 February 2007 by screening approximately 1.1 million newborns using tandem mass spectrometry analysis of underivatised blood spot samples to quantitate octancylcarnitine (C8). Follow-up biochemistry and mutation analyses for cases (mean triplicate C8 value >= 0.5 mu mol/L) were reviewed to confirm diagnosis. Ethnicity was ascertained from clinician report and denominators from 2001 UK Census estimates of ethnic group of children less than one year.Results Sixty-four infants were c.985A>G MCADD homozygotes (overall prevalence 5.8 per 100,000 live births; 95% Cl 4.4-7.2). Sixty (93%) were White, two (3%) were mixed/other and two were of unknown ethnic origin. No Asian or Black homozygotes were identified. Proportions of White, mixed/other, Asian and Black births in screening regions were estimated, yielding homozygous c.985A>G MCADD birth prevalence of 6.9 per 100,000 (95% Cl 5.2-8.8) in White, and 95% Cl estimates of 0-2.7 per 100,000 in Asian and 0-5.8 in Black populations. The c.985A>G carrier frequency in the White group was estimated at one in 65 (95% Cl 1/74, 1/61) under Hardy-Weinberg conditions.Conclusion c.985A>G homozygous MCADD is not found in Block and Asian ethnic groups that have been screened at birth in England. This is consistent with the earlier published observations suggesting that MCADD due to the c.985A>G mutation is a disease of White ethnic origin.