The Role of the Nephrologist in the Diagnosis and Follow-up of Patients with Fabry's Disease: The Importance of a Multidisciplinary Approach

Abstract

Fabry's disease (FD) is an X-linked lysosomal storage disorder caused by deficient activity of alpha-galactosidase A, resulting in the accumulation of the glycosphingolipid globotriaosylceramide (Gb3). FD is characterized by the involvement of several systems including the renal, neurological, cardiovascular, cochleovestibular, ocular, gastrointestinal and cutaneous systems. Hemizygous male individuals are primarily affected. Heterozygous females may display moderate to severe disease, which is likely related to the pattern of X-chromosome inactivation. There is a wide spectrum of FD severity. In the classic form of the disease, the clinical manifestations start in childhood and worsen over time according to the glycosphingolipid deposition. In a small percentage of patients with residual enzyme activity the onset of symptoms is late and affects mainly the heart (late-onset variants). Substrate storage affects the kidney, leading to nephropathy as one of the major complications of FD; this may occur in both sexes. These patients develop proteinuria and progress rapidly to chronic renal failure leading to end-stage renal disease. Enzyme replacement therapy and chaperone therapy have been demonstrated to improve the course of the disease, especially when started early. Since the diagnosis of FD is difficult to make, these elements put the nephrologist in a crucial position to diagnose the disease and identify patients who need specific therapy. A multidisciplinary approach is vital in the management of the disease. We describe the role of a multidisciplinary team in the diagnosis, treatment and follow-up of Fabry patients.