Test ID: AGAS
Alpha-Galactosidase, Serum

Detection of hemizygous affected males

Preferred screening specimen.

Fabry disease is an X-linked recessive lysosomal storage disorder with an incidence of at least 1 in 50,000 males. Fabry disease results from deficient activity of the enzyme alpha-galactosidase A (a-Gal A) and the progressive deposition of glycosylsphingolipids in tissues throughout the body, in particular, the kidney, heart, and brain.

Symptoms usually appear in childhood or adolescence and can include acroparesthesias (pain crises), multiple angiokeratomas, reduced or absent sweating, and corneal opacity. In addition, progressive renal involvement leading to end-stage renal disease typically occurs in adulthood followed by cardiovascular or cerebrovascular disease, or both.

Severity and onset of symptoms are dependent on the amount of residual enzyme activity. The classic form of Fabry disease occurs in males with <1% a-Gal A activity. Males with residual a-Gal A activity may present with either of 2 variant (renal or cardiac) forms of Fabry disease with onset of symptoms later in life. Individuals with the renal variant typically present in the third decade with the development of renal insufficiency and, ultimately, end-stage renal disease. These individuals may or may not share other symptoms with the classic form of Fabry disease. Individuals with the cardiac variant are often asymptomatic until they present with cardiac findings such as cardiomyopathy, mitral insufficiency, or conduction abnormalities in the fourth decade. The cardiac variant is not associated with renal failure.

Females with 1 mutation are referred to as carriers of Fabry disease and can have clinical presentations ranging from asymptomatic to severely affected and may have a-Gal A activity in the normal range. Therefore, additional studies including molecular genetic analysis (FABMS/88264 Fabry Disease, Full Gene Analysis) are recommended to detect carriers.

Mutations in the GLA gene are associated with Fabry disease. Disease-causing mutations have been identified in nearly 100% of males with clinical symptoms. Mutation analysis is the most reliable method to detect carrier females. Detection of ceramide trihexoside in urine sediment (CTSA/81979 Ceramide Trihexoside/Sulfatide Accumulation in Urine Sediment, Urine) and an ophthalmology examination to detect whorl-like corneal deposits or tortuosities of conjunctival vessels can further confirm a diagnosis of Fabry disease.

See Fabry Disease Testing Algorithm in Special Instructions.

0.074-0.457 U/L

Note: Results from this assay are not useful for carrier determination. Carriers usually have levels in the normal range.

Deficiency (<0.016 U/L) of alpha-galactosidase in properly submitted specimens is diagnostic for Fabry disease in males. If concerned about specimen integrity, please recheck using leukocyte testing (AGA/8785 Alpha-Galactosidase, Leukocytes).

Urine sediment analysis (CTSA/81979 Ceramide Trihexoside/Sulfatide Accumulation in Urine Sediment, Urine) for the accumulating trihexoside substrate is also recommended.

Carriers usually have alpha-galactosidase levels in the normal range.

See Fabry Disease Testing Algorithm in Special Instructions.

Carrier analysis is best done by molecular methods. Detection of ceramide trihexoside in urine sediment can also be used.

Carrier detection using the enzyme is unreliable, for this reason, consultation on detection of carriers is desirable.

See Fabry Disease Testing Algorithm in Special Instructions.

1. Desnick RJ, Ioannou YA, Eng CM: a-Galactosidase A deficiency: Fabry disease. In The Metabolic Basis of Inherited Disease. Vol 2. 7th edition. Edited by CR Scriver, AL Beaudet, WS Sly, D Valle. New York, McGraw-Hill Book Company, 1995, pp 2741-2784

2. Mehta A, Hughes DA: Fabry Disease. Available from http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=fabry Reviewed February 6, 2008

• Informed Consent for Genetic Testing
• Fabry Disease Testing Algorithm