Development of useful second-tier tests for newborn screening by tandem mass spectrometry

由于日本最近开始使用串联质谱法在全国范围内筛查新生儿遗传性代谢疾病，并且在健康新生儿的干血斑中测量的筛查标志物值的分布在筛查实验室之间差异很大，因此已经认识到质量保证体系的重要性。为了尽量减少假阴性病例，我们调整了实验室之间CPT 2缺乏症和甲基丙二酸血症的常规标志物和新标志物的截止值。我们还开发了对脂肪酸氧化障碍阳性病例的血清酰基肉毒碱分析，结合淋巴细胞脂肪酸氧化试验和串联质谱法，以及通过气相色谱-质谱法测量干血斑中有机酸的新方法，用于诊断B12-反应性甲基丙二酸血症、丙酸血症、异戊酸血症、葡萄糖酸血症和枫糖浆尿病。

As nation-wide newborn screening for inherited metabolic disorders using tandem mass spectrometry has been recently started in Japan, and distributions of measured screening marker values in dried blood spots of healthy newborns vary considerably among screening laboratories, the importance of quality assurance system has been recognized. In order to minimize false negative cases, we have adjusted the cut-off values for conventional markers and new markers for CPT2 deficiency and methylmalonic acidemia among laboratories. We also have developed the serum acylcarnitine analysis to the cases positive for fatty acid oxidation disorders, in combination with the fatty acid oxidation test using lymphocytes and tandem mass spectrometry, and the new methods to measure organic acids in dried blood spots by gas chromatography-mass spectrometry for the diagnosis of B12-responsive methylmalonic acidemia, propionic acidemia, isovaleric acidemia, glutaric acidemia and maple syrup urine disease.