Fabry disease

Fabry disease is a rare X-linked disorder of glycosphingolipid metabolism caused by a deficiency of the lysosomal acid hydrolase enzyme, alpha-galactosidase A. The resulting accumulation of substrate, mostly globotriaosylceramide, leads to a progressive, multiorgan disease affecting predominantly the kidneys, skin, heart, and nervous system. It is one of over 50 lysosomal storage diseases. It is typically diagnosed in young men after many years of ‘acral pain’ syndrome, when the diagnosis is made through identification of characteristic abnormalities of skin, kidney or heart, or of other organs. Renal failure has been a common outcome. Females may also develop manifestations, usually later in life. Renal biopsy shows vacuoles/deposits in podocytes and other renal cell types with progressive scarring. The diagnosis can be made by measuring enzyme levels in men, or by genetic testing. This latter is the more reliable test in women. Fabry disease can now be treated where affordable by regular (every 2 weeks) intravenous infusions of recombinant preparations of the deficient enzyme. These are burdensome and expensive, but are transforming the outlook for the condition.