Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
BMC Pediatr. 2010 Nov 17;10:82. doi: 10.1186/1471-2431-10-82.
Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of mitochondrial fatty acid oxidation and is one of the most common inborn errors of metabolism. Identification of MCADD via newborn screening permits the introduction of interventions that can significantly reduce associated morbidity and mortality. This study reports on the first three years of newborn screening for MCADD in Ontario, Canada.
Newborn Screening Ontario began screening for MCADD in April 2006, by quantification of acylcarnitines (primarily octanoylcarnitine, C8) in dried blood spots using tandem mass spectrometry. Babies with positive screening results were referred to physicians at one of five regional Newborn Screening Treatment Centres, who were responsible for diagnostic evaluation and follow-up care.
From April 2006 through March 2009, approximately 439 000 infants were screened for MCADD in Ontario. Seventy-four infants screened positive, with a median C8 level of 0.68 uM (range 0.33-30.41 uM). Thirty-one of the screen positive infants have been confirmed to have MCADD, while 36 have been confirmed to be unaffected. Screening C8 levels were higher among infants with MCADD (median 8.93 uM) compared to those with false positive results (median 0.47 uM). Molecular testing was available for 29 confirmed cases of MCADD, 15 of whom were homozygous for the common c.985A > G mutation. Infants homozygous for the common mutation tended to have higher C8 levels (median 12.13 uM) relative to compound heterozygotes for c.985A > G and a second detectable mutation (median 2.01 uM). Eight confirmed mutation carriers were identified among infants in the false positive group. The positive predictive value of a screen positive for MCADD was 46%. The estimated birth prevalence of MCADD in Ontario is approximately 1 in 14 000.
The birth prevalence of MCADD and positive predictive value of the screening test were similar to those identified by other newborn screening programs internationally. We observed some evidence of correlation between genotype and biochemical phenotype (C8 levels), and between C8 screening levels and eventual diagnosis. Current research priorities include further examining the relationships among genotype, biochemical phenotype, and clinical phenotype, with the ultimate goal of improving clinical risk prediction in order to provide tailored disease management advice and genetic counselling to families.
中链酰基辅酶 A 脱氢酶缺乏症（MCADD）是一种线粒体脂肪酸氧化紊乱，是最常见的先天性代谢缺陷之一。通过新生儿筛查发现 MCADD 可以引入显著降低相关发病率和死亡率的干预措施。本研究报告了加拿大安大略省新生儿筛查 MCADD 的头三年情况。
安大略省新生儿筛查于 2006 年 4 月开始通过串联质谱法对干血斑中的酰基肉碱（主要是辛酰肉碱，C8）进行定量检测来筛查 MCADD。筛查结果阳性的婴儿被转介到五个区域新生儿筛查治疗中心之一的医生处，由他们负责进行诊断评估和随访护理。
2006 年 4 月至 2009 年 3 月，安大略省约有 439000 名婴儿接受了 MCADD 筛查。74 名婴儿筛查阳性，C8 中位数为 0.68μM（范围 0.33-30.41μM）。31 名筛查阳性婴儿被确诊为 MCADD，36 名婴儿被确诊为未受影响。与假阳性结果（中位数 0.47μM）相比，MCADD 患儿的筛查 C8 水平更高（中位数 8.93μM）。29 例确诊 MCADD 患儿进行了分子检测，其中 15 例为常见的 c.985A>G 突变纯合子。常见突变的纯合子婴儿的 C8 水平（中位数 12.13μM）高于 c.985A>G 和第二个可检测突变的复合杂合子（中位数 2.01μM）。假阳性组中发现了 8 例确诊的突变携带者。MCADD 筛查阳性的阳性预测值为 46%。安大略省 MCADD 的估计出生患病率约为 1/14000。
MCADD 的出生患病率和筛查试验的阳性预测值与国际上其他新生儿筛查计划的结果相似。我们观察到基因型与生化表型（C8 水平）之间以及 C8 筛查水平与最终诊断之间存在一定的相关性。目前的研究重点包括进一步研究基因型、生化表型和临床表型之间的关系，最终目标是改善临床风险预测，以便为家庭提供个性化疾病管理建议和遗传咨询。
