Test ID: AGAS
Alpha-Galactosidase, Serum

Diagnosis of Fabry disease in males 

Preferred screening specimen.

Enzyme testing is useful in identifying affected males. Enzyme levels for carriers are usually within the normal range. Order FABMS/88264 Fabry Disease, Full Gene Analysis for carrier testing.

See Fabry Disease Testing Algorithm in Special Instructions.

• Informed Consent for Genetic Testing
• Fabry Disease Testing Algorithm

Fluorometric

Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic vial

Specimen Volume: 2 mL

Forms:

1.   1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.

2.   2. If not ordering electronically, submit a Biochemical Genetics Request Form (Supply T439) with the specimen.

Fabry disease is an X-linked lysosomal storage disorder resulting from deficient activity of the enzyme alpha-galactosidase A (alpha-Gal A) and the subsequent deposition of glycosylsphingolipids in tissues throughout the body; in particular, the kidney, heart, and brain. More than 150 mutations in the GLA gene have been identified in individuals diagnosed with Fabry disease. 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% alpha-Gal A activity. Symptoms usually appear in childhood or adolescence and can include acroparesthesias (pain crises in the extremities), 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 and cerebrovascular disease. The estimated incidence is 1 in 40,000 males.

Males with residual alpha-Gal A activity may present with either a renal or cardiac variant form 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. Variant forms of Fabry disease may be underdiagnosed.

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

Reduced or absent alpha-Gal A in blood spots, leukocytes (AGA/8785 Alpha-Galactosidase, Leukocytes), or serum (AGAS/8784 Alpha-Galactosidase, Serum) can indicate a diagnosis of classic or variant Fabry disease. Molecular sequence analysis of the GLA gene (FABMS/88264 Fabry Disease, Full Gene Analysis) allows for detection of the disease-causing mutation in affected patients and carrier detection in females.

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 detection using enzyme levels is unreliable; mutation analysis (FABMS/88264 Fabry Disease, Full Gene Analysis) is the recommended test.

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

2. De Schoenmakere G, Poppe B, Wuyts B, et al: Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients. Nephrol Dial Transplant 2008;23:4044-4048

3. Spada M, Pagliardini S, Yasuda M, et al: High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet 2006;79:31-40

4. Mehta A, Hughes DA: Fabry Disease. GeneReviews. Edited by RA Pagon, TD Bird, CR Dolan, et al. University of Washington, Seattle. Last updated March 2011

Alpha-galactosidase is a lysosomal enzyme active at an acidic pH. The enzyme hydrolyzes artificial substrates such as 4-methylumbelliferyl and alpha-D galactopyranoside. The 4-methylumbelliferone liberated is measured by fluorometry. (Desnick RJ, Allen KY, Desnick SJ, et al: Fabry's disease: enzymatic diagnosis of hemizygotes and heterozygotes. J Lab Clin Med 1973;81:157-171)

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