Fabry Disease

Question 1

Type 1 Fabry Disease overview

Answer 1

<1% Gal-A activity with NO functional enzyme
Missense, nonsense, splicing, frameshift
Prominent vascular endothelial GL-3 accumulation

Question 2

Type 1 Fabry phenotype

Answer 2

EARLY ONSET:

• eye changes (cornea)
• hypohidrosis
• pain
• skin lesions

LATER SYMPTOMS:

• cardiac disease
• cerebrovascular disease,
• renal failure

Question 3

Major sites of GL-3 accumulation

Answer 3

1. endothelial cells
   - ischemia and occlusion causes acroparesthesias, hypohydrosis, GI pain, angiokeratoma
2. cardiac cells
   - early diastolic dysfunction, LVH, mitral insufficiency, arrhythmias
3. Renal, podocytes, tubular cells

Question 4

Natural history of type 1 Fabry disease

Answer 4

0-15 years; pain, hypohidrosis, eye, intestinal symptoms
16+ - kidney, heart, brain, symptoms

Avg age of death (males) = 40
Avg age of death in females is more variable