| Co-Investigator(Kenkyū-buntansha) |
MORI Masataka Kumamoto University Medical School Institute of Medical Genetics Professor, 医学部, 教授 (40009650)
YAMASHITA Fumio Kurume University School of medicine Institute of Medical Genetics Professor, 医学部, 教授 (20080723)
KITAGAWA Teruo Nihon University School of Medicine Department of Pediatrics Professor, 医学部, 教授 (50058765)
NARISAWA Kuniaki Tohoku University School of Medicine Department of Biochemical Genetics Professo, 医学部, 教授 (90004647)
OYANAG Kazuhiko Sapporo Medical College Department of Pediatrics Associate Professor, 助教授 (10045388)
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| Research Abstract |
1. Retrospective survey of congenital hyperammonemia 154 patients with urea cycle disorders and 124 patients with organic acidemia, lysinuric protein intolerance, hyperonithinemia-hyperammonemia- homocitrullinemia syndrome and others accompanying with hyperammonemia were identified during 1978-1988 in Japan. Further detailed data were obtained from 95 and 69 patients of the former and the latter groups, respectively. OTC (Ornithine transcarbamylase) deficiency (X-linked inheritance) is the most common disease in urea cycle disorders (59 %), an incidence of which was estimated to be 1/50,000 to 80,000. It was found that an incidence of late onset type of male OTC deficiency is higher than hitherto considered, and the age of oldest onset was unexpectedly high, being 56-year-old. The most common of organic acidemia was methylmaronic acidemia and 58 patients with the disease were identified during the survey period.
2. Treatment of congenital hyperammonemia In addition to standard therapy;
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low protein diet and essential amino acids supplementation, L-carnitine administration was found to be effective in patients with OTC deficiency, CPS deficiency and organic acidemia.
3. Gene analysis of urea cycle disorders OTC deficiency: DNA analysis of one male patient with 0 percent of control activity revealed C to T substitution in exon 5, generating a stop codon in place of normal arginine at amino acids 109 of OTC protein. Analysis of other two male patients, of whom enzyme activities ranged from 16-19 % of control, revealed C to T substitution in exon 8, generating Trp to Arg at 277 of OTC protein. Arginase deficiency: DNA analysis of mutant enzyme in one patients with 0 percent of control activity revealed 4 base deletion in exon 3 in one allele and one base deletion in exon 2 in another allele, both of which generate stop codon at residue 132 and 31, respectively. Citrullinemia: Analysis of mutant arginino succinate synthetase gene of one patient with early onset revealed deletion of the exon 7 in one allele and C to T substitution at 310 residue in another allele, the latter generating Arg to Trp missense mutation. Less
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