Adrenoleukodystrophy; pathogenesis, diagnosis and therapy
| Project/Area Number |
62570420
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
TANAKA Kazuhiko Department of Pediatrics, assistant professor, Shiga University of Medical Science,, 医学部, 講師 (70135474)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Adrenoleukodystrophy / peroxisome / peroxisomal disorders / peroxisome / 脂肪酸β-酸化 / 極長鎖飽和脂肪酸 / 極長鎖不飽和脂肪酸 / cytoplasmic lamellar inclusion |
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| Research Abstract |
We used mass fragmentography to analyze a very long-chain fatty acid composition of erythrocyte membrane sphingomyelin. The content of hexacosanoic acid ( C26:0 ), tetracosanoic acid ( C24:0 ) and docosanoic acid ( C22:0 ) in adrenoleukodystrophy ( ALD ) hemizygotes and heterozygotes was significantly higher than in controls. Although the ration of C26:0 to c22:0 in 18 of the 46 controls was in the range of ALD heterozygotes, the absolute content of C26:0 and C24:0 in controls did not overlap with that of the ALD hemizygotes or heterozygotes. The content of C26:0 and C24:0 is more reliable for detection of ALD hemizygotes and heterozygotes than the ratio of C26:0 to C22:0 when red cell sphingomyelin is used for diagnosis.
Rectal mucosal biopsies were performed for seven members of five families with ALD. Many histiocytes contained characteristic cytoplasmic lamellar inclusions that were identical to those seen in adrenocortical cells, brain macrophages, and Schwann cells of affected patients. The ultrastructural features were seen in all patients and also in two asymptomatic younger brothers who had presymptomatic ALD according to assay of very long-chain fatty acids.
Fibroblasts obtained from two ALD patients were cultured with medium enriched in oleic acid ( C18:1 ) or erucic acid ( C22:1 ). when more than 30 um of C18:1 or C22:1 was added to cultured medium, total C26:0 concentration in fibroblasts from two ALD patients were lowered less than 63 % that of the control. Decreases in saturated very long-chain fatty acid lecels in cultured skin fibroblasts from ALD patients were accompanied by increases in the monounsaturated elongation products of C18:1 and c22:1.
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Report
(3 results)
Research Products
(10 results)
