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Test ID: AGAS Alpha-Galactosidase, Serum

Reporting Name

Alpha-Galactosidase, S

Useful For

Diagnosis of Fabry disease in male patients


Preferred screening test (serum) for Fabry disease

Clinical Information

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, in the kidney, heart, and brain. Variants within the GLA gene cause Fabry disease and more than 630 variants have been identified Severity and onset of symptoms are dependent on the amount of residual enzyme activity. The classic form of Fabry disease occurs in male patients who have less than 1% alpha-Gal A activity. Symptoms usually appear in childhood or adolescence and can include acroparesthesias (burning pain in the extremities), gastrointestinal issues, multiple angiokeratomas, reduced or absent sweating, corneal opacity, and proteinuria. In addition, progressive renal involvement leading to end-stage renal disease (ESRD) typically occurs in adulthood, followed by cardiovascular and cerebrovascular disease. The estimated incidence varies from 1 in 3,000 infants detected via newborn screening to 1 in 10,000 males diagnosed after onset of symptoms.


Male patients with residual alpha-Gal A activity greater than 1% may present with 1 of 3 variant forms of Fabry disease with onset of symptoms later in life: a renal variant associated with ESRD but without the pain or skin lesions; a cardiac variant typically presenting in the sixth to eighth decade with left ventricular hypertrophy, cardiomyopathy and arrhythmia, and proteinuria, but without ESRD; and a cerebrovascular variant presenting as stroke or transient ischemic attack. The variant forms of Fabry disease may be underdiagnosed.


Female patients who are carriers of Fabry disease can have clinical presentations ranging from asymptomatic to severely affected. Measurement of alpha-Gal A activity is not generally useful for identifying carriers of Fabry disease, as many of these individuals have normal levels of alpha-Gal A. Therefore, molecular genetic analysis of the GLA gene (FABRZ / Fabry Disease, Full Gene Analysis, Varies) is recommended to detect carriers.


Unless irreversible damage has already occurred, treatment with enzyme replacement therapy (ERT) has led to significant clinical improvement in affected individuals. In addition, some (adult) patients may be candidates for an oral chaperone therapy. For this reason, early diagnosis and treatment are desirable, and in a few US states early detection of Fabry disease through newborn screening has been implemented.


Absent or reduced alpha-Gal A in blood spots (AGABS / Alpha-Galactosidase, Blood Spot) , 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, Varies) allows for detection of the disease-causing variant in both male and female patients. The biomarkers globotriaosylsphingosine (LGB3S / Globotriosylsphingosine, Serum) and ceremide trihexosides (CTSA / Ceremide Trihexosides and Sulfatides, Urine) may be elevated in patients with Fabry disease and may aid in the diagnostic evaluation of female patients and in individuals with a variant of uncertain significance in GLA.


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


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

Testing Algorithm

The following algorithms are available in Special Instructions:

-Fabry Disease: Newborn Screen-Positive Follow-up

-Fabry Disease Diagnostic Testing Algorithm


For more information, see Newborn Screening Act Sheet Fabry Disease: Decreased Alpha-Galactosidase A in Special Instructions.

Analytic Time

8 days

Day(s) and Time(s) Performed


Clinical Reference

1. Desnick RJ, Ioannou YA, Eng CM: Alpha-Galactosidase A Deficiency: Fabry Disease. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, NY: McGraw-Hill; 2014. Accessed February 14, 2019. Available at

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. Mehta A, Hughes DA: Fabry Disease. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Updated 2013 Oct 17. University of Washington, Seattle  Accessed February 11, 2019. Available at

4. Laney DA, Bennett RL, Clarke V, et al: Fabry disease practice guidelines: recommendations of the National Society of Genetic Counselors. J Genet Couns 2013;22:555-564

5. Laney DA, Peck DS, Atherton AM, et al: Fabry disease in infancy and early childhood: a systematic literature review. Genet Med 2015;17(5)323-330

Method Name


Specimen Type


Advisory Information

Carrier detection using enzyme levels is unreliable for female patients as results may be within the normal values. Order FABRZ / Fabry Disease, Full Gene Analysis, Varies for testing carrier status.

Additional Testing Requirements

Urine sediment analysis (CTSA / Ceramide Trihexosides and Sulfatides, Urine) for the accumulating trihexoside substrate and measurement of globotriaosylsphingosine (LGB3S / Gobotriaosylsphingosine, Serum) are also recommended.

Necessary Information

Sex of patient is required for interpretation of results.

Specimen Required

Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic vial

Specimen Volume: 2 mL

Specimen Minimum Volume

0.2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Frozen (preferred) 14 days
  Refrigerated  24 hours

Reference Values

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.

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
AGAS Alpha-Galactosidase, S 1813-5


Result ID Test Result Name Result LOINC Value
50578 Specimen 31208-2
50579 Specimen ID 57723-9
50580 Source 31208-2
50581 Order Date 82785-7
50582 Reason For Referral 42349-1
50583 Method 49549-9
50590 Alpha-Galactosidase,S 1813-5
50584 Interpretation 59462-2
50585 Amendment 48767-8
50586 Reviewed By 18771-6
50587 Release Date 82772-5


1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Biochemical Genetics Patient Information (T602) in Special Instructions

3. If not ordering electronically, complete, print, and send an Inborn Errors of Metabolism Test Request (T798) with the specimen.

Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Cerebrovascular, mml-Pediatric, mml-Neurometabolic