Introduction
Authors: Ravi Thadhani
Journal: Journal of the American Society of Nephrology (2002)

This supplement of the Journal of the American Society of Nephrology is dedicated to Anderson-Fabry Disease (AFD), an X-linked lysosomal storage disorder that is the result of enzyme α-galactosidase A deficiency. This defect leads to the accumulation of incompletely metabolized glycosphingolipids in various organs, especially the kidney. Indeed, an important contributor to the morbidity and mortality of AFD is unrelenting progressive renal failure. Anderson-Fabry disease was initially described at the end of the 19th century. Today, just over 100 years after its initial description, we can boast about the development of specific enzyme replacement therapy to treat this devastating disorder. The last century of progress, beginning with the discovery of lysosomes and their function, followed by the uncovering of the genetic and enzymatic alterations that lead to organ pathology and clinical disease, and ending with the development of specific therapy, is a prime example of how science and technology change medical practice. Why should nephrologists concern themselves with AFD? Although the prevalence of AFD is low compared with diabetes and hypertension, which overwhelm our practices, the introduction of therapy that potentially halts and reverses progression toward renal failure is strong reason to take interest. Furthermore, there is little doubt that this condition is underdiagnosed. The care for patients with AFD certainly requires multiple specialties, but it especially requires a nephrologist who first entertains the diagnosis, is versed in the natural history, and is aware of the current therapeutic options. It is for this reason that in November of 2001 several nephrologists participated in a symposium in Cambridge, Massachusetts, entitled “Anderson-Fabry Disease: A Nephrology Perspective.” The spirited discussions that occurred during this day-long symposium reaffirmed that much remains to be learned despite the significant advances that have been made. The sections that follow highlight our current understanding of AFD and are written by those who have previously made original contributions to this field. We begin with two important introductory sections. These are followed by an overview of renal pathology and renal natural history and include the results from two recent clinical trials of enzyme replacement therapy that examined kidney histology and function. We end the renal section with the clinical aspects of end-stage renal disease among patients with AFD. The last two sections of this supplement provide a more detailed review of the cardiac and neurologic manifestations of AFD, also important contributors to the morbidity and mortality of patients with AFD. We hope this supplement provides a helpful summary of our current understanding of AFD and how this field, as it applies to nephrology, will unravel over the next few years. We dedicate this supplement to the biochemists, pathologists, molecular biologists, geneticists, clinicians, and of course the patients, all of whom have acted in concert to finally bring hope to those suffering from AFD. Ravi Thadhani has received a research grant from Transkaryotic Therapies, Inc., and now serves as a consultant for their Fabry Registry.