Initially Nondiagnosed Fabry's Disease when Electron Microscopy Is Lacking: The Continuing Story of Focal and Segmental Glomerulosclerosis
A kidney biopsy was performed in a 37-year-old man with proteinuria of 2.1 g/day, serum creatinine of 2.48 mg/dl and a glomerular filtration rate of 44 ml/min (table ). Optic microscopy revealed focal and segmental glomerulosclerosis (fig. ). The patient was started on meprednisone 40 mg/day, valsartan 320 mg/day and a gradual increase in aliskiren dose until 300 mg/day were reached. Low-sodium diet compliance was followed with urinary sodium excretion. One month later, serum creatinine increased to 2.7 mg/dl and proteinuria decreased to 0.8 g/day. Three months later, the steroid dose was tapered and the creatinine clearance improved to 54 ml/min and proteinuria remained steady for the following months (0.6–1 g/day). Twenty months later, while on dual blockade (valsartan had been lowered to 160 mg/day due to hypotension) and meprednisone 4 mg/day, proteinuria increased to 1.9 g/day. Steroids were restarted but proteinuria worsened to 6.8 g/day and creatinine clearance increased to 56 ml/min. A new kidney biopsy was performed and a test for α-galactosidase levels displayed low levels (0.7 ng/ml). A mutation [c.98A>G (D33G)] was identified in the gene of α-galactosidase A, diagnosed by sequential analysis. The kidney biopsy was consistent with secondary focal and segmental glomerulosclerosis and suggested Fabry's disease (fig. ). Electron microscopy and genetic studies confirmed the diagnosis (fig. ). The patient was started on agalsidase β (Fabrazyme, Genzyme Corp., Cambridge, Mass., USA) intravenously at 1 mg/kg body weight every fortnight and steroids gradually decreased, while the dual blockade was unchanged. Two months after diagnosis, his proteinuria decreased to 2.7 g/day, his creatinine clearance was 46 ml/min and steroids were discontinued. One month later, his proteinuria increased to 3 g/day and the creatinine clearance was 40 ml/min. As adjuvant therapy, meprednisone 10 mg was restarted and added to the regime. Proteinuria decreased to 2 g/day and creatinine clearance was 37 ml/min.