Fabry disease: renal biopsy-proven cases from China

Fabry disease is a rare metabolic disorder resulting from deficient activity of the lysosomal enzyme alpha-galactosidase A (alpha-GalA). Renal involvement is the major cause of morbidity and mortality in male patients. Here, we describe the largest series ever reported for this condition in China.

Nine patients were enrolled in this study. Routine light microscopy (including toluidine blue staining), immunofluorescence and electron microscopic examinations were performed. We measured alpha-GalA activity in leukocyte and gene mutation analysis. Clinical and laboratory data of the patients were collected.

Eight of the 9 patients were hemizygous males. Proteinuria was obvious in all patients. Three patients presented with mild renal function impairment. Light microscopy revealed glomeruli full of enlarged podocytes with abundant foamy cytoplasm. Toluidine blue stain revealed abundant cytoplasmic granular inclusions within the podocytes, tubular epithelial cells and endothelial cells of peritubular capillaries. Electron microscopy showed abundant electron-dense myelin figures within the podocyte cytoplasm. Arteriolar hyalinization and occlusion were also observed. Extrarenal manifestations, including acroparesthesia, hypohidrosis, abnormal electrocardiography and angiokeratoma were noted. No cornea verticillata or lenticular opacities were observed. These patients had about 0.3%-1.3% residual alpha-GalA activity in leukocytes. We identified a novel missense mutation (F273L) causing nonclassical Fabry disease.

Fabry disease is relatively rare in China. Renal biopsy and specific staining is efficacious in the correct diagnosis of the disease. Discrepancies in the clinical manifestations of Fabry disease (i.e., eye disorders and hypertension) exist between cases found in China and those detailed in Western reports.