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.
