Anderson-Fabry Disease: Its Place among Other Genetic Causes of Renal Disease

In the last two decades, decisive advances have been made in the field of human genetics, including renal genetics. The responsible genes have been mapped and then identified in most monogenic renal disorders by using positional cloning and/or candidate gene approaches. These approaches have been extremely efficient since the number of identified genetic diseases has increased exponentially over the last 5 years. The data derived from the Human Genome Project will enable a more rapid identification of the genes involved in the remaining “orphan” inherited renal diseases, provided their phenotypes are well characterized. We have entered the post-gene era. What is/are the function(s) of these genes? What are the molecular partners of the gene product? What is the disease mechanism, and how is the normal cascade of events disturbed when the gene is altered by a mutation? The main challenge in many renal genetic diseases, including autosomal dominant polycystic kidney disease (ADPKD), is to design pharmacologic means to complement/substitute or to bypass defective steps and thus modify the clinical course of the disease. These steps have been accelerated in a few genetic disorders, such as Anderson-Fabry Disease (AFD), including research on gene therapy.