Test Catalog

Interpretive Handbook

Test 89407 :
Alpha-Galactosidase, Blood Spot

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Fabry disease is an X-linked recessive lysosomal storage disorder resulting from deficient activity of the enzyme alpha-galactosidase A (a-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 less than 1% a-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 a-Gal A activity may present with either of 2 variant forms of Fabry disease (renal or cardiac) 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.


Enzyme replacement therapy became available for Fabry disease treatment in the early 2000s, which lead to significant clinical improvement unless irreversible damage had already occurred. For this reason, early detection of Fabry disease through newborn screening is expected to improve the outcome of affected patients and has recently been implemented in 2 US states. 


Females who are carriers of Fabry disease 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 of the GLA gene (FABRZ / Fabry Disease, Full Gene Analysis) are recommended to detect carriers.


Reduced or absent a-Gal A in blood spots, leukocytes (AGA / Alpha-Galactosidase, Leukocytes), or serum (AGAS / Alpha-Galactosidase, Serum) can indicate a diagnosis of classic or variant Fabry disease. Molecular sequence analysis of the GLA gene (FABRZ / 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.

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation of patients with a clinical presentation suggestive of Fabry disease


Follow-up to an abnormal newborn screen for Fabry disease

Interpretation Provides information to assist in interpretation of the test results

In male patients, results less than 1.2 nmol/mL/hour in properly submitted specimens are consistent with Fabry disease. Normal results (> or =1.2 nmol/mL/hour) are not consistent with Fabry disease.


In female patients, normal results (> or =2.8 nmol/mL/hour) in properly submitted specimens are typically not consistent with carrier status for Fabry disease; however, enzyme analysis, in general, is not sufficiently sensitive to detect all carriers. Because a carrier range has not been established in females, molecular genetic analysis of the GLA gene (FABRZ / Fabry Disease, Full Gene Analysis) should be considered when alpha-galactosidase A activity is less than 2.9 nmol/mL/hour, or if clinically indicated.


Pseudodeficiency results in low measured alpha-galactosidase A, but is not consistent with Fabry disease; GAAZ / Pompe Disease, Full Gene Analysis should be performed to resolve the clinical question.


See Fabry Disease Testing Algorithm in Special Instructions.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances


Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Males: > or =1.2 nmol/mL/h

Females: > or =2.8 nmol/mL/h

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Chamoles NA, Blanco M, Gaggioli D: Fabry disease: enzymatic diagnosis in dried blood spots on filter paper. Clin Chim Acta 2001;308:195-196

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. Matern D, Gavrilov D, Oglesbee D, et al: Newborn screening for lysosomal storage disorders. Semin Perinatol 2015 Apr;39(3):206-216

5. Mehta A, Hughes DA: Fabry Disease. In GeneReviews. Accessed 11/30/15. Available at URL: http://www.ncbi.nlm.nih.gov/books/NBK1292/