Association of renal ectopia with Fabry's disease in 3 patients.

PURPOSE: Fabry's disease is a rare, inherited lysosomal storage disorder characterized by decreased activity of the lysosomal hydrolase alpha-galactosidase A and impaired degradation of globotriaosylceramide, which accumulates in the lysosomes of virtually every cell in the body. Kidney damage is a prominent feature of the disease but to our knowledge renal ectopia as a comorbidity has not been previously reported. We present clinical and genetic features in 2 female and 1 male patient with Fabry's disease and renal ectopia. MATERIALS AND METHODS: The diagnosis of Fabry's disease was made by measuring alpha-galactosidase A activity in blood leukocytes and by mutational analysis of the alpha-galactosidase A gene. The anatomical location of the kidneys was defined by native and single bolus 3-phase coronal computerized tomography angiography. To determine the possible genetic association of Fabry's disease and renal ectopia we performed a genetic analysis of informative, closely linked microsatellite markers surrounding the gene. RESULTS: All patients carried the c.469C>T mutation in the alpha-galactosidase A gene, causing premature stop codon (Glu157X). In all 3 patients downward dislocation of the right kidney (pelvic kidney) was found in association with double renal arteries. We noted that a haplotype telomeric to the alpha-galactosidase A gene cosegregated with renal ectopia in 3 family members, suggesting the existence of a gene for X-linked renal ectopia in the region of DXS1001-DXS1073. CONCLUSIONS: To our knowledge this is the first report of an association of renal ectopia with Fabry's disease.

[Molecular pathology and clinical manifestations of Fabry disease]. / A Fabry-kór molekuláris patológiája és klinikai megjelenési formái.

Fabry disease is a rare, progressive lysosomal storage disorder caused by mutation in the GAL gene and an impaired function of the alpha-galactosidase A enzyme. The enzymatic defect results in the progressive accumulation of glycosphingolipids in endothelial cells, smooth muscle cells, leucocytes and fibroblasts leading to organ damage in the skin, eye, nervous system, kidney and heart. Major clinical manifestations include acroparesthesis, angiokeratoma, corneal opacities, vascular diseases of the heart, kidney, and the central nervous system. Enzyme replacement therapy has recently become available for the treatment of Fabry patients. In this review the authors describe clinical features of Fabry disease in 31 Hungarian patients. At the time of this analysis the database consisted of 31 cases (15 males, 16 females) of whom 5 have died (4 males, 1 female). The most common disease-specific manifestation was angiokeratoma in males, and eye symptoms in females. 25% of female subjects were symptom free. Genotyping was performed in all cases and disease-causing mutations were found in all families. Three new mutations were identified. Twelve patients (8 males and 4 females) are currently receiving enzyme replacement therapy.

The effect of frequent or occasional dialysis-associated hypotension on survival of patients on maintenance haemodialysis.

BACKGROUND: While frequent or occasional symptomatic intradialytic hypotension (IDH) may influence patient well-being, its effects on survival-independent of comorbidities-has not previously been investigated. In this study, therefore, our objective was to assess the effect of frequent IDH (f-IDH) or occasional IDH (o-IDH) on survival. METHODS: During a 10 month run-in period in 1998, 77 patients with f-IDH (> or =10 hypotensive events/10 months, responding only to medical intervention) and 101 patients with o-IDH (1 or 2 events/10 months) were identified among all 958 patients of a dialysis network. Eighty-five patients who had no hypotensive episodes (no-IDH) during this run-in phase served as controls. Patients were followed for a median of 27 months (range: 0.3-37) and survival of patients in the three groups was compared by log-rank test. Independent association of f-IDH and o-IDH with survival, compared with no-IDH, was assessed by a proportional hazards model that included patient demographics, laboratory data and antihypertensive medication as well as comorbidity. RESULTS: Forty-five patients (58%) with f-IDH, 47 (47%) with o-IDH and 33 (39%) with no-IDH died during the follow-up. Mortality rates (deaths/100 patient years) were 37 (log-rank P = 0.013 vs no-IDH), 26 (log-rank P = 0.375 vs no-IDH) and 21 in the three groups, respectively. This indicates significantly decreased survival in patients with f-IDH as compared to those with no-IDH. In multivariate proportional hazards regression, however, where age, sex, time spent on dialysis, presence of coronary heart disease, diabetes, Kt/V, albumin level and use of beta-blockers, calcium-channel blockers and long-acting nitrates has been adjusted for, neither f-IDH nor o-IDH was associated with survival. CONCLUSIONS: Mortality in patients with f-IDH is significantly higher than in those without such events. After adjustments for covariates, however, there is no independent effect of frequent or occasional episodes of IDH on mortality.