TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: AGAS    
Alpha-Galactosidase, Serum

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

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.

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

Serum is the preferred screening specimen for Fabry disease.

 

Enzyme testing is useful in identifying affected male patients.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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.

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

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 3000 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 (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 (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 (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 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.

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.

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.

Interpretation Provides information to assist in interpretation of the test results

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).

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

Individuals with pseudodeficiency allelic variants can show reduced alpha-galactosidase A enzyme activity with this assay.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. 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 November 24, 2020. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225546984

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: Pagon RA, Adam MP, Ardinger HH, et al: eds. GeneReviews [Internet]. . University of Washington, Seattle; 2002. Updated January 5, 2017. Accessed November 24, 2020. 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;22:555-564

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

6. Ferreira S, Auray-Blais C, Boutin M, et et al: Variations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma. Clin Chim Acta. 2015 Jul 20;447:96-104

Special Instructions Library of PDFs including pertinent information and forms related to the test