Fabry's disease pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
- Fabry disease is an X-linked inherited lysosomal storage disorder that is caused by a deficiency of alpha-galactosidase.
- Alpha-galactosidase is a lysosomal protein responsible for breaking down globotriaosylceramide, a fatty substance stored in various types of cardiac and renal cells.
- Mutations to the GLA gene encoding α-GAL may result in complete loss of function of the enzyme.
- When globotriaosylceramide is not properly catabolized, it is accumulated in cells lining blood vessels in the skin, cells in the kidney, heart, and nervous system. As a result, signs, and symptoms of Fabry disease begin to manifests.[1]
Genetics
- Fabry's disease follows an X-linked recessive inheritance pattern.
- A deficiency of the enzyme alpha galactosidase A causes a glycolipid known as globotriaosylceramide (also abbreviated as Gb3, GL-3, or ceramide trihexoside) to accumulate within the blood vessels, mononuclear phagocytes, neurons, other tissues, and organs.
- This accumulation leads to an impairment of their proper function. The condition affects hemizygous males, as well as both heterozygous and homozygous females; males tend to experience the most severe clinical symptoms, while females vary from virtually no symptoms to those as serious as males.
- This variability is thought to be due to X-inactivation patterns during embryonic development of the female.