Abstract: Recently, the increasing number of children with organic acidemias (OAs) and fatty acid oxidation defects (FAODs) has been detected with development of diagnostic tools, like GC/MS or MS/MS, for inborn metabolic disease (IMD). We have performed collaboration study with some Asian countries, and have noticed the diversity of disease contribution and genetic aspects. Diversity of disease distribution: metabolic screening of children at high risk using GC/MS and NS/MS has been performed in collaboration with several Asian countries. In India, Vietnam, and China, as well as Japan, methylmalonic acidemia (MMA) was most common, followed by urea cycle disorder (UCD), propionic academia (PPA). In Vietnam and India, 3-ketothiolase deficiency (BKTD), maple syrup urine disease (MSUD), and oxoprolinuria are also common, although they are extremely rare in Japan. In China, frequency of MMA seemed to be high, in particular combined MMA and homocystinuria many of which are B12 responsible. Genetic diversity: (I) MMA: in China, 42% of MMA are combined type of MMA and HCY due to CblC defect. 609G>A in MMACHC gene is a common mutation, covering 55%; (II) BKTD: in Vietnamese patients, c.662C>G in T2 gene is common, covering 72%; (III) PPA: in Japanese, Y435C mutation in PCCB gene is a common mutation in the mild form of PPA, at prevalence of 1 in 86 alleles in Japanese population; (IV) MCAD deficiency: common mutation 985A>C which covers about 90% of alleles among Caucasian is famous. A mutation study of Japanese cases, revealed a common mutation, c.449delCTGA, covering about 45% of the alleles. It is still unknown whether the mutation is Japanese specific, or East-Asian specific. Newborn mass screening (NBS) is increasingly popular in Asian countries. The diversity of disease distribution and genetic mutations will be made clear with the spread of collaboration studies and expanded NBS using MS/MS.
