Signs & Symptoms of Fabry Disease

Renal Impact	Cardiac Dysfunction
Cerebrovascular Complications	Pain
Angiokeratomas	Hypohidrosis/Anhidrosis
Ophthalmologic Findings	Heat and Cold Intolerance
Gastrointestinal Manifestations

Signs and symptoms associated with Fabry disease are widely varied, making diagnosis challenging. Clinical onset usually occurs in childhood or adolescence, but symptoms are frequently misinterpreted or overlooked.^[1] Accurate diagnosis is frequently not established until adulthood, when the disease has progressed, and organ dysfunction or failure has occurred.^[1]

The cardinal presenting features of Fabry disease are intermittent acroparesthesia and episodic crises of pain and fever (especially in childhood), angiokeratomas, hypohidrosis, heat and cold intolerance, and a characteristic “whorled” corneal opacity that does not affect vision. Progressive accumulation of GL-3 in the vascular endothelium and other tissues leads to life-threatening manifestations in adulthood involving the heart, kidneys, central and peripheral nervous system, and cerebrovascular system.^[2-4]

The list below provides an overview of the signs and symptoms of Fabry disease that may be seen at different stages of life. Both male and female patients may experience some or all of these manifestations to varying degrees, depending in part on the extent of alpha-GAL activity levels.^[1]

Childhood

• Episodic pain crises, acroparesthesia
• Hypohidrosis
• Corneal and lenticular opacities
• Recurrent fever
• Heat and cold intolerance

Adolescence

• Gastrointestinal manifestations
• Angiokeratomas
• Fatigue
• Episodic pain crises, acroparesthesia
• Hypohidrosis
• Corneal and lenticular opacities
• Recurrent fever
• Heat and cold intolerance

Adulthood

• Renal insufficiency/failure
• Neurological complications
• Cerebrovascular disease
• Cardiac dysfunction
• Hearing loss and tinnitus
• Gastrointestinal manifestations
• Angiokeratomas
• Fatigue
• Episodic pain crises, acroparesthesia
• Hypohidrosis
• Corneal and lenticular opacities
• Recurrent fever
• Heat and cold intolerance

Click on the links at the top of this page to learn more about selected signs and symptoms.

^References

1. Shelley ED, Shelley WB, Kurczynski TW. Painful fingers, heat intolerance, and telangiectases of the ear: easily ignored childhood signs of Fabry disease. Pediatr Dermatol. 1995;12:215-219.

2. Desnick RJ, Ioannou YA, Eng CM. Alpha-galactosidase A deficiency: Fabry disease. In: The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill, 2001;3733-3774.

3. Okuda S. Renal involvement in Fabry’s disease. Intern Med. 2000;39:601-602.

4. Grewal RP. Stroke in Fabry’s disease. J Neurol 1994;241:153-156.