1986 Fiscal Year Final Research Report Summary
Study on Biochemical Abnormalities of Congenital organic aciduria
| Project/Area Number |
59440045
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
TADA Keiya Tohoku University School of Medicine, 医学部, 教授 (20046907)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIZAWA Shinobu Tohoku University School of Medicine, 医学部附属病院, 講師 (60158748)
NARISAWA Kuniaki Tohoku University School of Medicine, 医学部, 助教授 (90004647)
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| Project Period (FY) |
1984 – 1986
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| Keywords | Organic acidemia / Multiple carboxylase deficiency / Ketotic hyperglycinemia / Lactic acidosis Propicnic acidemia / Methylmalonic acidemia / メチルグルタコン酸尿症 / 高乳酸血症 / チトクロームCオキシダーゼ欠損症 / ピルビン酸脱炭酸酵素欠損症 |
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| Research Abstract |
We studied on biochemical abnormalities of multiple carboxylase deficiency, ketotic hyperglycinemia ,methylglutaconic aciduria and lactic acidosis.
1)Multiple carboxylase deficiency: Fibroblasts and leukocytes from the patient were found to have a deficiency of ACC,cytosolic enzyme,as well as PCC,MCC and PC, which are mitochondrial enzymes. We suggested that the primary defect in this disorder was in the holocarboxylase synthetase. 2) Ketotic hyperglycinemia : We suggested that the reduction of the glycine cleavage system in the liver of ketotic hyperglycinemia occured secondarily and was caused mainly by a decrease of H-protein activity. 3) Methylglutaconic aciduria : We developed a new assay for 3 methylglutaconyl CoA hydratase in which the substrate,[5- <^(14)C> ]3-methylglutaconyl CoA,was synthesized using 3 methylcrotonyl CoA carboxylase. In the two patients the enzyme activities were 2[3% of normal. 4) Lactic acidosis: An enzymatic study of cultured skin fibroblasts was 56 patoents with lactic acidosis. In eight of the patients pyruvate decarboxylase (PDC) deficiency was found. The reduction of cytochrome c oxidase was demonstrated in six of the patients. It was suggested that the patients with severe PDC deficiency developed Leigh's disease but those with mild deficiency might not. Two siblings with cytochrome c oxidase deficiency was diagnosed as having Leigh's disease and seemed to be the first case of a generalized defect in cytochrome c oxidase.
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