Natural history of Fabry renal disease -: Influence of α-galactosidase A activity and genetic mutations on clinical course

We reviewed the medical records of 105 male patients with Fabry disease. We describe the clinical course and histology of their renal disease and correlate them with residual α-galactosidase A (α-gal A) activity and with mutations in the α-gal A gene. Hemizygous male patients with Fabry disease may develop proteinuria and chronic renal insufficiency in adolescence or early adulthood. By age 35 years, 50% of patients had non-nephrotic range proteinuria and almost 20% had early renal insufficiency. Fifty percent of surviving patients had renal insufficiency by age 42 years, and 50% had progressed to end-stage renal disease by age 47 years. Twenty-three percent of all patients eventually developed end-stage renal disease. By age 55 years, 50% of the patients had died, and all had died by age 60 years. Nephrotic proteinuria was present in 18% of patients and hypertension was present in 30% of patients. Either manifestation may appear before or after the onset of chronic renal insufficiency. After the onset of chronic renal insufficiency, the mean rate of change in glomerular filtration rate was -12.2 mL/min per year with patients reaching end-stage renal disease after 4.1 years. The presence of detectable residual α-gal A activity in peripheral leukocytes was associated with a later onset of chronic renal insufficiency, lower renal globotriaosylceramide content, and lower scores for renal histologic damage. Conservative missense mutations were associated with longer renal survival compared with nonconservative missense or other mutations.