Fabry disease (FD), the second most common type of
lysosomal storage disease (
LSD), is one of 41 disorders characterized by accumulation of substances normally degraded within lysosomes. It is an X-linked recessive disorder characterized by a deficiency of lysosomal
alpha-galactosidase A (alpha-Gal A). The locus for human alpha-Gal A is located on the Xq22 chromosome. Most FD mutations are confined to a single family. Although FD is an X-linked disorder, up to one third of female carriers develop clinical manifestations of the disease. It typically presents during infancy or adolescence with crisis of
neuropathic pain (acroparesthesia),
angiokeratomas, and asymptomatic corneal lesions. As Gb3 deposition progresses, clinical manifestations occur in other organs. Patients typically die in the fourth or fifth decade of life due to cardiac, renal or cerebrovascular complications. Usually, there is diffuse deposition of
glycosphingolipid in the renal glomeruli, tubules, interstitium, and vasculature. Clinically, the renal disease manifests with
hypertension, microscopic
hematuria (rare), moderate
proteinuria, which can be in the nephrotic range, and lipiduria.
End-stage renal disease can be treated with either dialysis or
transplantation. Thegene for (
x-Gal A was cloned and sequenced, which eventually led to production of
enzyme for
therapeutic use by either
recombinant DNA technology or gene activation.