Abstract

NATARIO, Ana; VIANA, Helena; GALVAO, Maria João  and  CARVALHO, Fernanda. Clinical and pathological findings in women withFabry disease. Port J Nephrol Hypert [online]. 2012, vol.26, n.1, pp.47-54. ISSN 0872-0169.

Introduction.Fabry disease is a rare metabolic disorder caused by the genetic deficiency of the lysosomalhydrolase alpha-galactosidase A, located on chromosome X. Females with the defective gene are more than carriers and can develop a wide range of symptoms. Nevertheless, disease symptoms generally occur later and are less severe in women than in men. The enzyme deficiency manifests as aglycosphingolipidosis with progressive accumulation ofglycosphingolipids and deposit of inclusion bodies inlysosomes giving a myelinlike appearance. Patients and Methods.Records of renal biopsies performed on adults from 1^st January 2008 to 31^st August 2011, were retrospectively examined at the Renal Pathology Laboratory. We retrieved biopsies diagnosed withFabry disease and reviewed clinical and laboratory data and pathology findings. Results.Four female patients with a mean age of 49.3 ±4.5 (44-55) years were identified. The mean proteinuria was 0.75± 0.3 g/24h (0.4-1.2) and estimatedglomerular filtration rate (CKD EPI equation) was 71 ±15.7 ml/min/1.73m 2 (48-83). Three patients experienced extra-renal organ involvement (cerebrovascular, cardiac, dermatologic, ophthalmologic and thyroid) with distinct severity degrees. Leukocyte α-GAL A activity was below normal range in the four cases but plasma and urinary enzymatic activity was normal. Light microscopy showed predominant vacuolization of thepodocyte cytoplasm and darkly staining granular inclusions on paraffin and plastic-embedded semi-thin sections. Electron microscopy showed in three patients the characteristic myelin-like inclusions in thepodocyte cytoplasm and also focal podocyte foot process effacement. In one case the inclusions were also present in parietalglomerular cells, endothelial cells ofperitubular capillary and arterioles. Conclusion. Clinical signs and symptoms are varied and can be severe among heterozygous females with Fabry disease. Intracellular accumulation of glycosphingolipids is a characteristichistologic finding of Fabry nephropathy. Since this disease is a potentially treatable condition, its early identification is imperative. We should consider it in the differential diagnosis of any patient presenting with proteinuria and/or chronic kidney disease, especially if there is a family history of kidney disease.

Keywords : Fabry disease; glomerulopathy; renal biopsy.

        · text in English     · English ( pdf )