Fabry Disease

Abstract

Fabry disease is a rare lysosomal storage disorder, caused by the deficiency of the enzyme alpha-galactosidase A that is responsible for the degradation of the sphingolipid globotriaosylceramide, also called Gb3. Due to the insufficient activity of alpha-galactosidase A, Gb3 accumulates in a variety of cells of the body, resulting in progressive organ damage. Fabry disease is an X-linked disorder in which also females are affected, although often less severely than males. Clinically, this multisystemic disorder is characterized by neuropathic pain, gastrointestinal disturbances, typical skin lesions, sweating difficulties, and kidney and heart failure. Life expectancy is significantly reduced, whereby in both males and females, renal and cardiac diseases are the primary causes of death. In children, pain in hands and feet (acroparesthesia) and abdominal cramps are the leading symptoms; further clinical manifestations include corneal opacities, called cornea verticillata, and skin abnormalities (angiokeratoma). Albuminuria and an increased heart size represent the first signs of renal and cardiac manifestation that can be present already in young patients. Besides symptomatic and supplementary treatment such as analgesics, drugs for kidney dysfunction and for blood pressure control, enzyme replacement therapy is available for children with Fabry disease.