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Abstract：
Early detection of congenital disorders by newborn screening (NBS) programs is essential to prevent or limit disease manifestation in affected neonates. These programs balance between the detection of the highest number of true cases and the lowest number of false-positives. In this case report, we describe four unrelated cases with a false-positive NBS result for very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD). Three neonates presented with decreased but not deficient VLCAD enzyme activity and two of them carried a single heterozygous ACADVL c.1844G>A mutation. Initial biochemical investigations after positive NBS referral in these infants revealed acylcarnitine and organic acid profiles resembling those seen in multiple acyl-CoA dehydrogenase deficiency (MADD). Genetic analysis did not reveal any pathogenic mutations in the genes encoding the electron transfer flavoprotein (ETF alpha and beta subunits) nor in ETF dehydrogenase. Subsequent further diagnostics revealed decreased levels of riboflavin in the newborns and oral riboflavin administration normalized the MADD-like biochemical profiles. During pregnancy, the mothers followed a vegan, vegetarian or lactose-free diet which probably caused alimentary riboflavin deficiency in the neonates. This report demonstrates that a secondary (alimentary) maternal riboflavin deficiency in combination with reduced VLCAD activity in the newborns can result in an abnormal VLCADD/MADD acylcarnitine profile and can cause false-positive NBS. We hypothesize that maternal riboflavin deficiency contributed to the false-positive VLCADD neonatal screening results.
摘要：
通过新生儿筛查（NBS）计划早期发现先天性疾病对于预防或限制受影响新生儿的疾病表现至关重要。这些程序在检测最高数量的真实病例和最低数量的假阳性之间取得平衡。在这个案例报告中,我们描述了4例无关的病例,NBS结果为超长链酰基辅酶A脱氢酶缺乏症(VLCADD)的假阳性.3例新生儿VLCAD酶活性降低但没有缺陷，其中2例携带单个杂合ACADVLc.1844G>A突变。这些婴儿的NBS转诊阳性后的初步生化检查显示，酰基肉碱和有机酸谱与多种酰基辅酶A脱氢酶缺乏症（MADD）相似。遗传分析未发现编码电子转移黄素蛋白（ETFα和β亚基）的基因或ETF脱氢酶中的任何致病性突变。随后的进一步诊断显示新生儿中核黄素水平降低，口服核黄素使MADD样生化谱正常化。在怀孕期间,母亲们跟着一个素食主义者，素食或无乳糖饮食可能导致新生儿消化性核黄素缺乏症。该报告表明，继发性（饮食）母体核黄素缺乏症与新生儿VLCAD活性降低相结合，可导致VLCADD/MADD酰基肉碱异常，并可导致假阳性NBS。我们假设母体核黄素缺乏导致VLCADD新生儿筛查结果假阳性。
