Newborn screening in Japan: restructuring for the new era.

Nationwide neonatal mass screening for inherited metabolic diseases has started in Japan since 1977. At least 8000 children have probably been spared from handicaps resulting from such diseases over the past 30 years. Recently remarkable changes have been made to the evolving neonatal screening system. Declining birth rate and economic problems in Japan have demanded a more effective neonatal screening system. Development of new innovative screening methods and treatment tools, e.g. tandem mass spectrometry (MS/MS) technology and enzyme replacement therapy for mucopolysaccharidosis (MPS), have facilitated expansion of target diseases in neonatal screening. We have carried out pilot screening using MS/MS in 6 laboratories in Japan. The incidence of inherited metabolic diseases was found to be 1 in 9330 (65 cases out of 606,380 babies screened) during the period between 1997 and 2007. The incidence was lower than those of Europe or USA (about 1 in 4000 to 5000). The disease frequency between unscreened symptomatic cases and asymptomatic cases detected through MS/MS screening were also found to be different. In MS/MS screening, the most common organic acidemia was propionic acidemia, whereas in symptomatic cases, methylmalonic acidemia was the most common. Further study of ethnic diversity in severity of propionic academia is required. The outcomes of patients detected in the MS/MS screening were significantly favourable. The results showed the benefits of MS/ MS screening. The diagnostic support network for gas chromatography-mass spectrometry (GC/ MS) analysis and enzyme determination has also been developed. We have developed an automated system of GC/MS data processing and auto-diagnosis which allowed the GC/MS data processing to be extremely fast and simple. Enzyme evaluation for diagnostic support for screening, including a method using peripheral blood and high performance liquid chromatography (HPLC), and another method of in-vitro probe assay using cultured cells and MS/MS. Furthermore, re-location of screening laboratories for a more efficient screening network will be required such that at least 30,000 samples can be analysed in each laboratory.