Test ID: AGA
Alpha-Galactosidase, Leukocytes

Diagnosis of Fabry disease in males  

Verifying abnormal serum alpha-galactosidase results in males with a clinical presentation suggestive of Fabry disease

Diagnosis of Fabry disease in males  

Useful to verify abnormal serum alpha-galactosidase results in males with a clinical presentation suggestive of Fabry disease.

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

Fabry disease is an X-linked lysosomal storage disorder that results from a deficiency of the enzyme alpha-galactosidase A (GLA; ceramide trihexosidase). Reduced GLA activity results in the accumulation of glycosphingolipids in the lysosomes of both peripheral and visceral tissues. Primarily affected are the skin, kidney, eyes, nervous system, and heart.

Severity and onset of symptoms of Fabry disease are dependent on the amount of residual GLA activity in the cells. Males with <1% GLA activity have the classic form of Fabry disease. Symptoms may present in childhood or adolescence with acroparesthesias (pain crises) and proteinuria. Multiple angiokeratomas, reduced or absent sweating, corneal opacity, renal insufficiency leading to end-stage renal disease, and cardiac and cerebrovascular disease occur later. Males with residual GLA activity may present with 1 of 2 variant forms of Fabry disease where onset of symptoms occurs later in life, typically in the third or fourth decade. These 2 forms can be described as "renal" and "cardiac" variants. The most prominent feature of the renal form is the development of renal insufficiency and, ultimately, end-stage renal disease. Individuals with the cardiac variant are often asymptomatic until they present with cardiac findings such as cardiomyopathy or mitral insufficiency in the fourth decade. The cardiac variant is not associated with renal failure. 

Mutations in the GLA gene are associated with Fabry disease. Disease-causing mutations have been identified in nearly 100% of males with clinical symptoms. Females with 1 mutation are referred to as carriers of Fabry disease, have clinical presentations ranging from asymptomatic to severely affected, and may have GLA activity in the normal range; therefore, mutation analysis (FABMS/88264 Fabry Disease, Full Gene Analysis) is the most reliable method to detect females who carry a mutation. Detection of ceramide trihexoside in urine sediment (CTSA/81979 Ceramide Trihexoside/Sulfatide Accumulation in Urine Sediment, Urine) can also be useful. An eye examination is useful to detect tortuousities of conjunctival vessels or whorl-like corneal deposits.

 
See Fabry Disease: Newborn Screen-Positive Follow-up algorithm and Fabry Disease Testing Algorithm in Special Instructions.

> or =23.1 nmol/hour/mg protein

An interpretative report will be provided.

Note: Results from this assay do not reflect carrier status because of individual variation of alpha-galactosidase enzyme levels.

Deficiency of alpha-galactosidase A (GLA) is diagnostic for Fabry disease in males.

Carrier females may have GLA results within the normal range.

 
See Fabry Disease: Newborn Screen-Positive Follow-up algorithm and 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.

Desnick RJ, Ioannou YA, Eng CM: Alpha-galactosidase A deficiency: Fabry disease. In The Metabolic and Molecular Bases of Inherited Disease (OMMBID), 8th edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, available at URL: www.ommbid.com. Accessed 2010

• Informed Consent for Genetic Testing
• Fabry Disease Testing Algorithm
• Fabry Disease: Newborn Screen-Positive Follow-up