Signs, Symptoms & Clinical Presentation

Renal impact Cerebrovascular Complications Angiokeratoma Ophthalmologic Findings Gastrointestinal Manifestations

Cardiac Dysfunction Pain Hypohidrosis/Anhidrosis Heat and Cold Intolerance

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. 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), angiokeratoma, 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, 3, 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

Angiokeratoma

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

Angiokeratoma

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.