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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

 

This test is not useful for patients undergoing a work up for a meat or meat-derived product allergy.

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 glycosphingolipids in tissues throughout the body; in particular, in the kidney, heart, and brain. Disease-causing variants within the GLA gene cause Fabry disease. 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 kidney failure typically occurs in adulthood, followed by cardiovascular and cerebrovascular disease.

 

Male patients with residual alpha-Gal A activity greater than 1% are at risk for a late-onset form of Fabry disease. Clinical manifestations may include adult-onset cardiac disease with left ventricular hypertrophy, cardiomyopathy, arrhythmia, and proteinuria; kidney failure without skin lesions or pain; or cerebrovascular disease presenting as stroke or transient ischemic attack. The variant forms of Fabry disease may be underdiagnosed.

 

Female patients with Fabry disease can have clinical presentations ranging from asymptomatic to severely affected. Measurement of alpha-Gal A activity is not generally useful for identifying female individuals with Fabry disease, as many of them will have normal levels. Therefore, molecular genetic analysis of the GLA gene (GLA / Fabry Disease, GLA Gene Sequencing with Deletion/Duplication, Varies) is recommended.

 

Unless irreversible damage has already occurred, treatment with enzyme replacement therapy has led to significant clinical improvement in affected individuals. In addition, some (adult) patients may be candidates for 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 (PLSD / Lysosomal and Peroxisomal Disorders Screen, Blood Spot), leukocytes (AGAW / 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 (GLA / Fabry Disease, GLA Gene Sequencing with Deletion/Duplication, Varies) allows for detection of the disease-causing variant in both male and female patients. The biomarkers globotriaosylsphingosine (LGB3S / Globotriosylsphingosine, Serum) and ceremide trihexosides (CTSU / Ceramide Trihexosides and Sulfatides, Random, Urine) are typically elevated in symptomatic patients with Fabry disease and may aid in the diagnostic evaluation of female patients and individuals with a variant of uncertain significance in GLA.

 

For more information see Fabry Disease Testing Algorithm and Fabry Disease: Newborn Screen-Positive Follow-up

Interpretation

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 (AGAW / Alpha-Galactosidase, Leukocytes).

Testing Algorithm

The following algorithms are available:

-Fabry Disease: Newborn Screen-Positive Follow-up

-Fabry Disease Diagnostic Testing Algorithm

 

If the patient has abnormal newborn screening results for Fabry disease, refer to the appropriate ACMG Newborn Screening ACT Sheet.(1)

Report Available

2 to 5 days

Day(s) Performed

Tuesday, Friday

Clinical Reference

1. ACMG Newborn Screening ACT Sheets. Accessed October 10, 2025. Available at www.acmg.net/ACMG/Medical-Genetics-Practice-Resources/ACT_Sheets_and_Algorithms/ACMG/Medical-Genetics-Practice-Resources/ACT_Sheets_and_Algorithms.aspx?hkey=9d6bce5a-182e-42a6-84a5-b2d88240c508

2. Desnick RJ, Ioannou YA, Eng CM. Alpha-galactosidase A deficiency: Fabry disease. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed October 10, 2025. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225546984

3. Mehta A, Hughes DA. Fabry disease. In: Adam MP, Feldman J, Mirzaa GM, et al. eds. GeneReviews [Internet]. University of Washington, Seattle; 2002. Accessed October 10, 2025. Available at www.ncbi.nlm.nih.gov/books/NBK1292/

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(5):555-564. doi:10.1007/s10897-013-9613-3

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. doi:10.1038/gim.2014.120

6. Ferreira S, Auray-Blais C, Boutin M, et al. Variations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma. Clin Chim Acta. 2015;447:96-104. doi:10.1016/j.cca.2015.06.003

7. Nowak A, Beuschlein F, Sivasubramaniam V, Kasper D, Warnock DG. Lyso-Gb3 associates with adverse long-term outcome in patients with Fabry disease. J Med Genet. 2022;59(3):287-293. doi:10.1136/jmedgenet-2020-10733

Method Name

Fluorometric

Specimen Type

Serum


Ordering Guidance


If testing is needed for assessment of meat or meat-derived product allergy, order either ALGAL / Galactose-Alpha-1,3-Galactose (Alpha-Gal), IgE, Serum or APGAL / Galactose-Alpha-1,3-Galactose (Alpha-Gal) Mammalian Meat Allergy Profile, Serum.

 

Enzyme testing is unreliable for female patients as results may be within the normal values even in affected female patients; order GLA / Fabry Disease, GLA Gene Sequencing with Deletion/Duplication, Varies.



Additional Testing Requirements


Urine sediment analysis for the accumulating trihexoside substrate and measurement of globotriaosylsphingosine are recommended. Order both CTSU / Ceramide Trihexosides and Sulfatides, Random, Urine and LGB3S / Globotriaosylsphingosine, Serum in conjunction with this test.



Necessary Information


Sex of patient is required for interpretation of results.



Specimen Required


Supplies: Sarstedt Aliquot Tube, 5 mL (T914)

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 2 mL serum

Collection Instructions: Centrifuge and aliquot serum into a plastic vial.


Specimen Minimum Volume

Serum: 0.3 mL

Specimen Stability Information

Specimen Type Temperature Time
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 female 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. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

82657

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
50590 Alpha-Galactosidase,S 1813-5
50584 Interpretation 59462-2
50586 Reviewed By 18771-6

Forms

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:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Biochemical Genetics Patient Information (T602)

3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Cerebrovascular, mml-Pediatric, mml-Neurometabolic