Hall Patricia L, Wittenauer Angela, Hagar Arthur
Emory Genetics Laboratory, Department of Human Genetics, Emory University, Atlanta, GA, United States.
Department of Human Genetics, Emory University, Atlanta, GA, United States.
Mol Genet Metab. 2014 Dec;113(4):274-7. doi: 10.1016/j.ymgme.2014.10.007. Epub 2014 Oct 16.
Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is a fatty acid oxidation disorder included on newborn screening (NBS) panels in many regions that have expanded to using tandem mass spectrometry for acylcarnitine screening. False positive (FP) screening results for MCAD deficiency have previously been linked to very low birth weight (VLBW) infants and those who are heterozygous for the common mutation, p.K324E. Previous studies have identified these causes of FP screens by sequencing residual dried blood spots. From our cohort of FP screens in Georgia, we identified an elevation at the same mass as octenoylcarnitine (C8:1) causing elevations of octanoylcarnitine (C8) not due to MCAD deficiency. We reviewed biochemical results from 2011 to 2013 for all newborn screens positive for MCAD deficiency in Georgia to identify screening criteria to allow these cases to be identified prospectively, thus saving families the stress of additional testing on their newborn and reducing healthcare costs while improving screening performance for the screening program. We identified the C8/C8:1 ratio as an effective marker, and developed criteria that will reduce FP screening results due to this interfering substance.
中链酰基辅酶A脱氢酶（MCAD）缺乏症是一种脂肪酸氧化障碍疾病，在许多已扩展至使用串联质谱法进行酰基肉碱筛查的地区，该疾病被纳入新生儿筛查（NBS）项目。此前，MCAD缺乏症的假阳性（FP）筛查结果与极低出生体重（VLBW）婴儿以及常见突变p.K324E的杂合子有关。以往的研究通过对残留干血斑进行测序，确定了这些导致FP筛查结果的原因。在我们佐治亚州的FP筛查队列中，我们发现与辛烯酰肉碱（C8:1）质量相同的物质升高，导致辛酰肉碱（C8）升高，而这并非由MCAD缺乏症引起。我们回顾了2011年至2013年佐治亚州所有MCAD缺乏症筛查呈阳性的新生儿的生化结果，以确定筛查标准，以便前瞻性地识别这些病例，从而减轻家庭对新生儿进行额外检测的压力，降低医疗成本，同时提高筛查项目的筛查性能。我们确定C8/C8:1比值为一个有效的标志物，并制定了标准，以减少由这种干扰物质导致的FP筛查结果。
