Adrenoleukodystrophy; pathogenesis, diagnosis and therapy

肾上腺脑白质营养不良;

• 批准号: 62570420
• 负责人: TANAKA Kazuhiko
• 金额: $ 0.96万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570420/
• 关键词: 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

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.

我们使用质量碎片分析法来分析红细胞膜鞘磷脂的长链脂肪酸组成。肾上腺脑白质营养不良(ALD)半合子和杂合子中二十二烷酸(C26:0)、二十四烷酸(C24:0)和二十二烷酸(C22:0)的含量显着高于对照组。尽管46个对照中有18个的C26:0与c22:0的比例在ALD杂合子范围内，但对照中C26:0和C24:0的绝对含量与ALD半合子或杂合子不重叠。当使用红细胞鞘磷脂进行诊断时，C26:0和C24:0的含量对于检测ALD半合子和杂合子比C26:0与C22:0的比例更可靠。对5名成员中的7名进行了直肠粘膜活检患有 ALD 的家庭。许多组织细胞含有特征性的细胞质层状包涵体，与受影响患者的肾上腺皮质细胞、脑巨噬细胞和施万细胞中所见的包涵体相同。所有患者以及根据极长链脂肪酸测定，在症状前患有 ALD 的两名无症状弟弟中均观察到超微结构特征。从两名 ALD 患者获得的成纤维细胞用富含油酸 (C18:1) 或富含油酸 (C18:1) 的培养基培养芥酸（C22:1）。当培养基中添加超过30μm的C18:1或C22:1时，两名ALD患者的成纤维细胞中的总C26:0浓度比对照降低了不到63%。 ALD 患者培养的皮肤成纤维细胞中饱和超长链脂肪酸水平的减少伴随着 C18:1 和 c22:1 的单不饱和伸长产物的增加。

项目成果

Kazuhiko Tanaka,et al.: Acta Pediatr.Jap.(1989)

田中和彦 (Kazuhiko Tanaka) 等：Acta Pediatr.Jap.(1989)

田中和彦 他: 日本小児科学会雑誌. 93. (1989)

Kazuhiko Tanaka 等人：日本儿科学会杂志 93。（1989）

Kazuhiko Tanaka et al.: "Electronmicroscopic study on biopsied rectal mucosa in adrenoleukodystrophy." Neurology. 37. 1012-1015 (1987)

Kazuhiko Tanaka 等人：“肾上腺脑白质营养不良症直肠粘膜活检的电子显微镜研究。”

Kazuhiko Tanaka: Neurology. 37. 1012-1015 (1987)

田中和彦：神经病学。

Kazuhiko,Tanaka et al.: Acta.Pediatr.Jap.(1989)

Kazuhiko,Tanaka 等人：Acta.Pediatr.Jap.(1989)