Deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier (AGC), encoded by the SLC25A13 gene on chromosome 7q21.3, causes autosomal recessive disorders: adult-onset type II citrullinemia (CTLN2) and neonatal hepatitis associated with intrahepatic cholestasis (NICCD). So far, we have described 12 SLC25A13 mutations: 11 were from Japan and one from Israel. Three mutations found in Chinese and Vietnamese patients were the same as those in Japanese patients. In the present study, we identified a novel mutation IVS6+1G>C in a Japanese CTLN2 patient and widely screened 12 SLC25A13 mutations found in Japanese patients in control individuals from East Asia to confirm our preliminary results that the carrier frequency was high in Asian populations. Mutations 851-854del and 1638-1660dup were found in all Asian countries tested, and 851-854del associated with 290-haplotype in microsatellite marker D7S1812 was especially frequent. Other mutations frequently detected were IVS11+1G>A in Japanese and Korean, S225X in Japanese, and IVS6+5G>A in Chinese populations. We found a remarkable difference in carrier rates in China (including Taiwan) between north (1/ 940) and south (1/48) of the Yangtze River. We detected many carriers in Chinese (64/4169 = 1/65), Japanese (20/1372 = 1/69) and Korean (22/2455 = 1/112) populations, suggesting that over 80,000 East Asians are homozygotes with two mutated SLC25A13 alleles.

The cblC type of combined methylmalonic aciduria (MMA) and homocystinuria (HC) is the most common inborn error of vitamin B 12 metabolism and is caused by mutations in the MMACHC gene. To elucidate the spectrum of mutations that causes combined MMA and HC in Chinese patients, the MMACHC gene was sequenced in 79 unrelated Chinese patients. Sequence analysis identified 98.1% of disease alleles and found that all patients had at least one MMACHC mutation. A total of 24 mutations were identified. Out of the 24 mutations identified, 9 were novel ones, including missense mutations (c.365A4T and c.452A4G), nonsense mutations (c.315C4G and c.615C4A), deletions (c.99delA and c.277-3_c.303del30), duplications (c.248dupT and c.626dupT) and an insertion (c.445_446insA). The c.609G4A, c.658_660delAAG, c.482G4A, c.394C4T and c.80A4G mutations were the most common mutations and accounted for 80% of disease alleles. Haplotype analysis suggests that the spread of the c.80A4G, c.609G4A and c.658_660delAAG mutations in Chinese patients were caused by a founder effect. The results indicate that defects occurring in the MMACHC gene are the major cause of this disease in Chinese patients with combined MMA and HC, and direct mutation analysis can therefore be used as a rapid confirmatory diagnosis among these Chinese patients.

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Newborns with significant neonatal jaundice (SNJ) would admit for evaluation and/or intervention due to an earlier or more rapid increase in bilirubin level. Bilirubin-induced neurological dysfunction in this population might be underestimated. We aimed to investigate the risk of long-term neurodevelopmental sequelae of SNJ in Taiwan. An SNJ 2000–2003 follow-up cohort consisting of 66,983 neonates was extracted from the nationwide, population-based health insurance database in Taiwan to survey the accumulative incidence of long-term (7-year) neurodevelopmental sequelae in comparison to a reference general-population neonate cohort of 12,579 individuals born in 2000. The SNJ follow-up cohort was furtherly categorized into subgroups according to interventions (phototherapy, intensive phototherapy, and exchange transfusion). The SNJ follow-up cohort exhibited significantly higher cumulative rates of long-term neurodevelopmental sequelae than did the reference cohort (P < 0.05). The risks of infantile cerebral palsy, hearing loss, and developmental delay in the SNJ follow-up cohort were between twice and three times of those in the reference cohort after adjusting for gender, comorbid perinatal disorders and urbanization levels. All intervention subgroups demonstrated higher risks for long-term neurodevelopmental sequelae than the reference cohort (P < 0.05) after adjustment. Patients with SNJ are at risk of developing neurodevelopmental disorders during their growth period. A scheduled follow-up protocol of physical and neurodevelopmental assessment during early childhood for these SNJ patients would potentially be helpful for the early detection of and intervention for neurodevelopmental disorders.

In spite of the increased incidence rates, the rates of mortality and kernicterus in patients with NJ significantly declined in Taiwan. The public health prevention programme, clinicians' awareness and effective management might contribute to the reduction of these acute severe sequelae.