Fabry Disease Progression

The accumulation of glycosphingolipids in visceral tissues throughout the body is progressive, and over time can become life-threatening. In order to provide the most appropriate supportive care after a diagnosis is made, it is recommended that patients be carefully assessed for evidence of renal, cardiac, or neurological involvement.

Potential clinical progression

Fabry disease manifestations may progressively worsen over time as GL-3 continues to accumulate in tissues throughout the body.

Symptoms
Childhood
Adolescence
Adulthood
Episodic pain crises
Acroparesthesia
Hyphidrosis/anhidrosis
Corneal and lenticular opacities
Recurrent fever
Heat and cold intolerance
Psychosocial manifestations
Proteinuria

Gastrointestinal distress

Angiokeratomas

Fatigue

Renal insufficiency


Neurological complications


Cerebrovascular disease


Cardiac dysfunction


Hearing loss and tinnitus


More about the signs and symptoms 

Renal dysfunction

Progressive glycosphingolipid deposition in the kidneys results in proteinuria and progressive renal dysfunction that can begin in adolescence.1 Gradual deterioration of renal function, leading to uremia and hypertension, may finally progress to end-stage renal disease.

Birefringent lipid deposits in kidney glomeruli

atrophic and hyalinized glomeruli characteristic of end-stage renal disease in a patient with Fabry disease

Light micrograph of a patient with Fabry disease shows characteristic birefringent glycosphingolipid deposits. The section was stained with Sudan Black B and observed under polarized light. Used with permission from R.J. Desnick, MD, Phd.

More about renal manifestation 

Cardiac dysfunction

Cardiac involvement is variable, but increases in severity with age. Progressive functional deficits may include left ventricular hypertrophy, valvular disease, premature coronary artery disease, angina, myocardial infarction, conduction abnormalities, arrhythmias, and congestive heart failure.1-2

More about cardiac dysfunction 

Cerebrovascular complications

In adolescents and adults, vascular accumulation of glycosphingolipids may lead to early ischemic stroke due to thrombosis of small arteries.3 Other complications may include hemiplegia, hemianesthesia, and transient ischemic attacks.

More about neurological manifestations 

Learn about the genetics of Fabry disease 

References:

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

2. Linhart A, T Palecek, J Bultas, et al. New insights in cardiac structural changes in patients with Fabry's disease. Am Heart J. 2000;139:1101-1108.

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