Renal pathology in Fabry disease
Renal pathology in Fabry disease
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DOI：
10.1097/01.asn.0000016684.07368.75
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发表时间：
2002-06-01
影响因子：
13.6
通讯作者：
Kopp, JB
中科院分区：
文献类型：
--
作者：
Alroy, J;Sabnis, S;Kopp, JB
法布里病是一种X-连锁隐性溶酶体贮积病，由溶酶体酶α-半乳糖苷酶A（α-Gal A）（一种切割末端α-半乳糖残基的酶）的活性缺陷引起。这种缺乏导致具有末端α-半乳糖残基的鞘糖脂（特别是神经酰胺三己糖基（Gb 3））在溶酶体中进行性蓄积。Gb 3在许多细胞中积累，特别是在肾上皮细胞、内皮细胞、周细胞、血管平滑肌细胞、心肌细胞和自主神经系统的神经元中（1）。遗传缺陷发生在所有细胞类型中，但在不同器官和细胞类型中的参与程度差异很大。这种异质性可能反映了鞘脂代谢的不同速率。因此，由于不同细胞回收的底物的类型和量，α-Gal A活性防止Gb 3蓄积的最低阈值要求在不同细胞类型中不同（2）。肾损害见于半合子（男性）和杂合子（女性）患者。后者的肾脏症状通常较轻，延迟2 - 30年，但变异性相当大（3）。变异性可能是X灭活的随机性质的结果，导致携带者之间和（至少理论上）一个携带者个体在不同组织或单个组织的区域中α-Gal A活性的显著变异性。
Fabry disease is an X-linked recessive lysosomal storage disease that is caused by deficient activity of the lysosomal enzyme α-galactosidase A (α-Gal A), an enzyme that cleaves terminal α-galactosyl residues. This deficiency results in progressive lysosomal accumulation of glycosphingolipid with terminal α-galactosyl residues, particularly globotriaosylceramide (Gb3). Gb3 accumulates in many cells, particularly in renal epithelial cells, endothelial cells, pericytes, vascular smooth muscle cells, cardiomyocytes, and neurons of the autonomic nervous system (1).The genetic defect occurs in all cell types, but involvement differs greatly among different organs and cell types. This heterogeneity likely reflects different rates of sphingolipid metabolism. Thus the minimum threshold requirement for α-Gal A activity to prevent Gb3 accumulation varies across cell types due to the type and amount of substrates that are recycled by the different cells (2). Renal lesions are found in both hemizygous (male) and heterozygous (female) patients. Renal symptoms in the latter are typically milder and delayed by 2 to 3 decades, but there is considerable variability (3). The variability is likely the result of the random nature of X inactivation, resulting in considerable variability in α-Gal A activity among carriers and (at least theoretically) within one carrier individual among various tissues or regions of a single tissue.