What is Fabry Disease?

• X-linked recessive glycolipid storage disease
• Caused by deficient activity of the lysosomal enzyme alpha-galacosidase A, resulting in the accumulation of globotriaosylceramide (a type of fat) in lysosomes in multiple cell types throughout the body
• Numerous mutations have been found in the alpha galactosidase-A (GLA) gene on the long arm of the X-chromosome (Xq22)
• Males are more severely affected; most heterozygous females are also affected though usually at a later age
• Clinical manifestations vary and include cutaneous, corneal, cardiac, renal, and neurologic manifestations
• Cutaneous manifestations: 
• angiokeratomas: vascular papules typically distributed in the inguinal, hip, and periumbilical areas
• hypohidrosis: decreased ability to sweat
• Corneal manifestations: 
• dry eye with whirl-like corneal deposits, cream-colored capsular deposits, faint posterior capsular opacity with a branching radial pattern
• Cardiac manifestations:  
• Left ventricular hypertrophy, aortic and mitral regurgitation, conduction defects, coronary artery disease, hypertension, aortic root dilation
• Males are more severely affected and life expectancy is decreased by approximately 20 years if untreated 
• Heterozygous females are typically affected at a later age and life expectancy is decreased by approximately 15 years if untreated
• Renal manifestations:
• Occur in 50% of male patients and 20% of female patients
• Principal findings are proteinuria and progressive renal insufficiency
• Neurologic manifestations:
• Peripheral neuropathy: recurrent discomfort of hands and feet with burning pain in plans and soles which can be severe and lead to suicide attempts; usually decreases with age
• Cerebrovascular complications: stroke often occurs before renal and cardiac manifestations