Recent Findings in Genetic and Enzymatic Analysis of Newborn Screening-Positive Subjects Based on Tandem Mass Spectrometry

Beginning 2014, all newborns living in Japan will have newborn screening (NBS) using tandem mass spectrometry (MS/MS). We participated in a pilot study for this new NBS initiative and provided diagnoses in cooperation with Hiroshima University and other facilities. Here, we introduce the information that we obtained. Medium-chain acyl-CoA dehydrogenase deficiency (MCADD), ACADM mutations found among Japanese patients are quite different from those of Caucasian patients. We estimated MCAD activities of 11 mutants found among Japanese patients and positively screened babies using molecular genetics methods. Some mutations were destructive, but others found by NBS maintained activities to a certain degree. Regarding methylmalonic academia (MMA), we found the first Japanese patient with isolated methylmalonic acidemia caused by a cblD defect. Unfortunately, he was negative in the NBS and developed acute metabolic decompensation during an acute illness. We found MMADHC mutation heterozygously in this patient. Through our study, we offered reliable data for most of the positively screened newborns and their family members through our original enzymatic assay using peripheral blood mononuclear cells. We also obtained beneficial information from these investigations. In order to raise the quality of the newly introducing MS/MS-NBS system in Japan, it is essential to achieve accurate diagnosis through a combination of enzymatic and genetic evaluation.

Keywords: Medium-chain Acyl-Coa dehydrogenase deficiency, Methylmalonic academia, Tandem mass spectrometry, Newborn screening.