FABRY DISEASE

By Gary M. White, MD


Fabry disease (FD), also known as angiokeratoma corporis diffusum, is an X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. Diffuse angiokeratomas of the skin result.

Diagnosis

The diagnosis may be confirmed by measuring the enzymatic levels of alpha-galactosidase, alpha-fucosidase, and alpha-sialidase (e.g., from skin fibroblast homogenates). Prenatal diagnosis is possible.

Fabry Disease in Women

Research seems to indicate that many women who carry the gene do develop symptoms. Of 303 women in the Fabry Outcome Survey, 77% experienced neurological symptoms such as pain, and 59% had cardiac manifestations such as left ventricular hypertrophy and palpitations FabryCommunity. For diagnosis in women, genetic analysis must be conducted in the event of a negative enzyme assays result. Genomic DNA and total RNA can be extracted from peripheral blood leukocytes or cultured skin fibroblasts.

Clinical

Onset of this condition is typically in childhood. The patient develops angiokeratomas in the distribution of a bathing suit. Angiokeratomas appear as red/purple dots. Anhidrosis and hypohidrosis also occur. Patients develop a characteristic and unusual symptom of painful, burning palms often described as "burning, sharp, pins-and-needles-like." Bouts of pain are often accompanied by a fever.

Multiple systemic abnormalities occur, e.g., myocardial infarctions, chest pain, dysrhythmias, renal failure, cerebrovascular accident, seizures, and cerebral hemorrhage. There is often an intolerance to heat or cold and the inability to sweat as well as high-frequency neurosensory hearing loss. Slit-lamp examination shows posterior capsular spokes, termed cornea verticillata. Maltese crosses may be seen in the urine.

The primary cause of death is renal, and without renal transplantation or dialysis the mean age of death is about 40 years. Cardiac events are another source of mortality.

Treatment

Fabrazyme, an enzyme replacement for the human enzyme alpha-galactosidase A, has been approve by the FDA for treatment in the US. It can decrease pain, increase the ability to sweat, improve the tolerance to temperature change, and improve cardiac function etc. Enzyme replacement therapy should begin as soon as possible.

Various other treatments are needed and usually carried out by non-dermatologists.

References

Indian J Dermatol Venereol Leprol 2008;74:389-91

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