Chronic renal failure and proteinuria in adulthood:: Fabry disease predominantly affecting the kidneys
Chronic renal failure and proteinuria in adulthood:: Fabry disease predominantly affecting the kidneys
复制标题
DOI：
10.1053/j.ajkd.2005.01.036
复制
发表时间：
2005-05-01
影响因子：
13.2
通讯作者：
Neumann, HPH
中科院分区：
文献类型：
--
作者：
Cybulla, M;Schaefer, E;Neumann, HPH
自从引入酶替代疗法以来，法布里病的预后发生了变化。因此，早期诊断是必要的。我们描述了一个家族，表现为慢性肾功能衰竭和蛋白尿，其中经典的皮肤和神经功能的特点是缺席和法布里病的诊断是困难的，直到第二个家庭成员发展肾脏异常。一名35岁男性因超重和高血压入院，血清肌酐水平为1.3 mg/dL（115 μ mol/L），蛋白排泄量为870 mg/d。因为一个兄弟，谁死了几年前在32岁的急性髓性白血病，也有慢性肾功能衰竭和蛋白尿，诊断法布里病被受理。在索引患者中，不存在提示法布里病的肢端感觉异常、多汗、疼痛、皮肤血管角化瘤和角膜轮动。相反，肾活检显示典型的神经酰胺三己糖苷沉积，白细胞α-半乳糖苷酶（α-GLA）A活性降低。对α-GLA基因的分析显示突变E66 K。在另一个无症状的30岁兄弟身上也发现了这种突变，他也有慢性肾衰竭和蛋白尿，但肾外检查结果正常。在死亡的兄弟中，法布里病，由于癌症相关的发现而在尸检中被遗漏，在反复审查组织学切片后可以得到证实。突变携带者还包括母亲、一个姐妹（两人都没有异常）和一个侄子（脚有阵发性疼痛）。我们的结论是家族性慢性肾功能衰竭合并蛋白尿提示Fabry病，而E66 K等特异性突变可能主要影响肾脏。
The prognosis of Fabry disease has changed since enzyme-replacement treatment was Introduced. Therefore, early diagnosis Is Instrumental. We describe a family presenting with chronic renal failure and proteinuria in which classic skin and neurological features were absent and the diagnosis of Fabry disease was difficult and not established until a second family member developed renal abnormalities. A 35-year-old man was admitted because he was overweight and had hypertension, with a serum creatinine level of 1.3 mg/dL (115 μ mol/L) and protein excretion of 870 mg/d. Because 1 brother, who died years ago at the age of 32 years of acute myeloid leukemia, also had chronic renal failure and proteinuria, the diagnosis of Fabry disease was entertained. In the Index patient, acroparesthesia, hypohidrosis, pain, angiokeratomas of the skin, and cornea verticillata suggesting Fabry disease were absent. Conversely, renal biopsy showed typical globotriaosylceramide deposits, and leukocyte a-galactosidase (α-GLA) A activity was decreased. Analysis of the α-GLA gene showed the mutation E66K. The mutation also was found In another asymptomatic 30-year-old brother who also had chronic renal failure and proteinuria, but normal extrarenal findings. In the brother who died, Fabry disease, missed at autopsy because of cancer-related findings, could be confirmed after repeated review of histological slides. Mutation carriers also included the mother, a sister (both without abnormalities), and a nephew (with episodic pains In his feet). We conclude that familial chronic renal failure combined with proteinuria Is suggestive of Fabry disease, and such specific mutations as E66K predominantly may affect the kidneys.