Fabry's disease a genetic disorder (X-linked recessive) due to the absence of the enzyme
alpha-galactosidase A. The disease is characterized by abnormal collections of glycolipids
in cells (histiocytes) within blood vessel walls, tumors on the thighs, buttocks, and
genitalia, decreased sweating, tingling sensations in the extremities, and cataracts.
Patients with Fabry 's disease die from complications of the kidney, heart, or brain.
The objective of this study is to test the belief that patients with Fabry's disease have a
problem with blood vessels becoming larger. The walls of blood vessels contain muscles that
when they relax the vessel becomes larger. This process is referred to as vasodilation. It
is controlled by a substance released by cells in blood vessels called EDRF
(endothelium-derived relaxing factor).
Several drugs can affect vasodilation. Researchers believe some drugs may work by blocking
the affect of EDRF. Researchers would like to test the effects of these drugs on the blood
vessels of normal volunteers and patients with Fabry's disease.
Fabry disease is a systematic genetic disease in which patients have abnormal blood vessels,
and leads to numerous complications including cerebrovascular strokes. The objective of
this study is to test the hypothesis that patients with Fabry disease have abnormal
endothelial-derived vasodilation. If found to be abnormal, endothelial-derived vasodilation
will serve as a useful clinical outcome measure in the evaluation of the efficacy of
specific treatment of Fabry disease, and possibly of other causes of cerebrovascular stroke.
The endothelium modulates vascular tone by the release of contracting and relaxing
substances that act on the underlying smooth muscle. It has been previously demonstrated
that patients with essential hypertension have a blunted vascular response to acetylcholine
(an endothelium-dependent vasodilator). In the present study, we shall analyze the regional
vascular responses to acetylcholine and sodium nitroprusside alone, and in the presence of
L-NMMA (an inhibitor of the synthesis of EDRF by endothelial cells) in 12 patients with
Fabry disease and 12 normal age matched control subjects. We will infuse drugs into the
brachial artery and will measure the responses of the forearm vasculature by means of strain
gauge plethysmography. Forearm blood flow and vascular resistance at baseline and after
infusion of vasoactive drugs, in Fabry patients, will be compared to the responses obtained
in the healthy control population. This study will be performed with collaboration of Dr.
Julio A. Panza, Senior Clinical Investigator from the Cardiology Branch, NHLBI.
Male patients with the classic form of Fabry disease, aged 18-50.
Normal male volunteers of the same approximate age will be included as a control.
No patients or volunteers with hypertension, hypercholesterolemia, diabetes, peripheral
vascular disease, coagulopathy, or any other disease predisposing to vasculitis or
No volunteers who are taking any kind of medication.
Must be able to give informed consent.