Fabry disease is a fat storage disorder caused by a deficiency of an enzyme involved in
the biodegradation of lipids. The gene that is altered in this disorder is on the
X-chromosome, so only the mother needs to be a carrier to produce an affected child. Her
sons have a 50 percent chance of having the condition, and her daughters have a 50 percent
chance of being a carrier. Some of the female carriers exhibit signs of the condition,
especially cloudiness of the cornea. In addition to the eye manifestations, males
characteristically have burning sensations in their hands and feet that is worse with
exercise and hot weather. Most of the males have small, raised, reddish-purple blemishes
on their skin. As they grow older, they may have impaired arterial circulation leading to
early heart attacks and strokes. The kidneys become progressively involved, and many
patients have required kidney transplantation or dialysis. A number of patients have
gastrointestinal difficulties characterized by frequent bowel movements shortly after
eating. This disorder is due to a deficiency of a lipid breakdown enzyme known as ceramidetrihexosidase,
also called alpha-galactosidase A. Its function is to cleave to a molecule of
galactose from a lipid that arises primarily from old red blood cells.
Fabry's Disease Treatment
The pain in the hands and feet usually responds to medications such as Tegretol
(carbamazepine) and dilantin. Gastrointestinal hyperactivity may be treated with
metoclopramide or Lipisorb® (a nutritional supplement). Recent experiments indicate that
enzyme replacement is effective therapy for patients with this disorder.
Enzyme replacement therapy to treat Fabry's Disease
In two independent reports at the annual meeting of the American Society of Human
Genetics, researchers reported successfully resolving Fabry disease symptoms with an
infusion of a normal, human enzyme once every 2 weeks.
The enzyme, [alpha]-galactosidase, is now being made by two competing U.S.
pharmaceutical companies. Based on the results of the two separate studies reported at the
meeting, both companies have submitted licensing applications to the Food and Drug
Administration under the Orphan Drug law, and expect a ruling this year. About 2,500
patients in the United States have Fabry disease.
The pathophysiology of Fabry disease centers on the accumulation of glycolipids that
cannot be metabolized, and, instead, become deposited in the vascular endothelium. This
eventually leads to damage of the skin, heart, and kidneys.
The results from one of the studies reported at the meeting--a 58-patient,
placebo-controlled trial--documented that after 20 weeks of enzyme replacement therapy,
the stored glycolipid completely disappeared from the renal vasculature in 20 of 29
treated patients. In contrast, none of the 29 patients treated with placebo infusions had
clearance of their blood vessels, reported Dr. Christine M. Eng of Baylor College of
Medicine in Houston.
Family Pratice News,
March 1, 2001
What is the prognosis for Fabry's Disease
Patients with Fabry disease usually survive into adulthood, but they are at risk for
strokes, heart attacks, and kidney damage. It is anticipated that enzyme replacement and
eventually gene therapy will eliminate these difficulties.