Fabry病的临床表现及肾脏病理学特征

Clinical manifestations and renal pathological features in patients with Fabry's disease

目的 :探讨Fabry病患者临床表现及肾组织形态学特点。 方法 :总结 9例Fabry病患者临床表现和肾组织形态学特点。同时对肾小球足细胞数定量分析 ,并借助足细胞特殊标记物WT1对足细胞的密度及其缺失分布特点进行观察。 结果 :①患者以年轻男性为主 ,多有肾脏病家族史。②多伴有Fabry病肾外表现 ,表现为皮肤血管角质瘤、少汗、低热、肢端感觉异常等症状。心脏受累发生率较高 ,多表现为房室传导阻滞、PR间期缩短、ST段和T波的异常、左心室高电压等。③均无明显角膜混浊、视网膜动脉曲张等Fabry病常见眼部病变。④肾脏病变表现为轻至中度蛋白尿。部分患者伴轻微镜下血尿。肾小管间质损伤较突出。⑤肾组织形态学改变表现为光镜下肾小球足细胞弥漫空泡变性 ;甲苯胺蓝染色显示足细胞浆内含大量嗜甲苯胺蓝的蓝色颗粒状物 ;电镜下嗜锇性、同心圆样髓样小体在胞浆中堆积。多数患者小管间质中重度病变。肾间质血管病变现象较为突出。⑥肾小球足细胞计数及足细胞密度均明显低于正常 (P <0 0 1) ,WT1表达缺失呈节段分布 ,缺失部位多位于周边袢和有节段硬化病变处。 结论 :①Fabry病以男性青年多见 ,多有肾脏损害的家族史。②多数患者存在肾外表现 ,心脏病变发生率较高。③无明显Fabry病特征性眼部病变 ,无明显?

Objective:To investigate the clinical manifestations and pathological characteristics of Fabry's disease. Methodology:The clinical manifestations and pathological characteristics of nine patients had been analyzed. The average number of podocyte per glomerulus was counted.Immunoflurecence doulbe-staining using anti-WT1, a marker of podocyte, and type Ⅳ collagen α3 chain were performed to illustrate the density of podocyte and the structure of glomerular basement membrane. Results:①Males are most dominating patients.Six patients are positive family history of kidney disease.②Five patients presented with extrarenal manifestations, including acroparesthesia (recurrent burning pain in the hands and feet), hypohidrosis (lack of sweating), low fever and characteristic skin lesions. Five patients have abnormal ECG and 2 patients of them have left ventricular hypertrophy. Cornea verticilata and lenticular opacities were not observed in all the patients.③Proteinuria , usually in the non-nephrotic range was obviously noted in the patients. Renal tubular function test including NAG enzyme as well as RBP were abnormal in the most of the patients.④By light microscopy, the glomerular enlargement and vacuolization of the epithelial cells. Toluidine blue stain appears abundant cytoplasmic granular inclusions within podocytes. Electron microscopy shows abundant electron-dense myelin figures within the podocyte cytoplasm. There are visible damages in the tubulointerstitium and vascular .Vascular involvement includes arteriolar hyalinization, incrassation , occlusion.⑤Patients with Fabry's disease much more podocytes loss than the normal .Lower WT1 expression was observed in all of these patients and segmental loss of podocyte markers on the edge of non-sclerotic glomerulus. Conclusion:①Fabry's disease is not rare in Chinese patients . A large percentage of the group has male. The most of patients are positive family history.②The extrarenal manifestations of Fabry's disease are seen in the most of patients. Cardiac syndrome is the most significant clinical features.③In all the patients,cornea verticilata, lenticular opacities and hypertension were not observed.④Proteinuria and chronic renal insufficiency were obvious clinical manifestation of renal damage in patients. Compared with primary renal disease , there is no especial clinical examination for Fabry's disease.⑤Renal pathology, toluidine blue staining and electron microscopical examination are very important means in the diagnosis of Fabry's disease.⑥Podocyte injury is the primary reason of renal lesions. The damage of tubulointerstitium and vascular is the important cause of renal lesions.