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HelpTest Code AGABS Alpha-Galactosidase, Blood Spot
Reporting Name
Alpha-Galactosidase, BSUseful For
Diagnosis of Fabry disease in male patients using blood spot specimens
Verifying abnormal serum alpha-galactosidase results in male patients with a clinical presentation suggestive of Fabry disease
Follow-up to an abnormal newborn screen for Fabry disease
This test is not useful for patients undergoing a workup for a meat or meat-derived product allergy.
Testing Algorithm
This test provides diagnostic testing for male patients with positive newborn screen results, positive family history, or clinical signs and symptoms suspicious for Fabry disease.
The following algorithms are available:
-Fabry Disease Diagnostic Testing Algorithm
-Fabry Disease: Newborn Screen-Positive Follow-up
If the patient has abnormal newborn screening results for Fabry disease. Refer to the appropriate ACMG Newborn Screening ACT Sheet.(1)
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
Whole bloodOrdering Guidance
If testing 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.
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
Additional studies including molecular genetic analysis of the GLA gene (FABRZ / Fabry Disease, Full Gene Analysis, Varies) are recommended to detect carriers.
Necessary Information
Provide a reason for testing with each specimen.
Specimen Required
Supplies: Card-Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Blood spot collection card
Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper and Whatman Protein Saver 903 paper
Specimen Volume: 2 blood spots
Collection Instructions:
1. Do not use device or capillary tube containing EDTA to collect specimen.
2. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.
3. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
4. Do not expose specimen to heat or direct sunlight.
5. Do not stack wet specimens.
6. Keep specimen dry.
Additional Information:
1. For collection instructions, see Blood Spot Collection Instructions
2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)
3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)
Specimen Minimum Volume
1 Blood spot
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Whole blood | Ambient (preferred) | 90 days | FILTER PAPER |
| Frozen | 90 days | FILTER PAPER | |
| Refrigerated | 90 days | FILTER PAPER |
Special Instructions
- Informed Consent for Genetic Testing
- Fabry Disease Diagnostic Testing Algorithm
- Fabry Disease: Newborn Screen-Positive Follow-up
- Biochemical Genetics Patient Information
- Blood Spot Collection Card-Spanish Instructions
- Blood Spot Collection Card-Chinese Instructions
- Informed Consent for Genetic Testing (Spanish)
- Blood Spot Collection Instructions
Reference Values
Males: ≥1.2 nmol/mL/hour
Females: ≥2.8 nmol/mL/hour
An interpretive report will be provided.
Day(s) Performed
Thursday
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 |
|---|---|---|
| AGABS | Alpha-Galactosidase, BS | 55908-8 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 50883 | Specimen | 31208-2 |
| 50884 | Specimen ID | 57723-9 |
| 50885 | Source | 31208-2 |
| 50886 | Order Date | 82785-7 |
| 50887 | Reason For Referral | 42349-1 |
| 50888 | Method | 85069-3 |
| 50889 | Alpha-Galactosidase, BS | 55908-8 |
| 50890 | Interpretation | 59462-2 |
| 50891 | Amendment | 48767-8 |
| 50892 | Reviewed By | 18771-6 |
| 50893 | Release Date | 82772-5 |
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, the kidney, heart, and brain. Variants within the GLA gene cause Fabry disease with severity and symptom onset 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 (formerly end-stage renal disease) 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 male patients diagnosed after onset of symptoms.
Measurement of alpha-Gal A in blood spots, leukocytes (AGAW / Alpha-Galactosidase, Leukocytes), or serum (AGAS / Alpha-Galactosidase, Serum) can reliably diagnose classic or variant Fabry disease in males. 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 kidney variant associated with kidney failure 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 kidney failure; and a cerebrovascular variant presenting as stroke or transient ischemic attack. The variant forms of Fabry disease may be underdiagnosed. Molecular genetic analysis of the GLA gene (FABRZ / Fabry Disease, Full Gene Analysis, Varies) allows for confirmation of a diagnosis of classic of variant Fabry disease in affected male patients with reduced alpha-Gal A activity.
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 will have normal levels. Therefore, molecular genetic analysis of the GLA gene (FABRZ / Fabry Disease, Full Gene Analysis, Varies) is recommended as the most appropriate diagnostic test to detect asymptomatic or symptomatic female carriers.
The biomarkers globotriaosylsphingosine (LGB3S / Globotriaosylsphingosine, Serum) and ceramide trihexosides (CTSU / Ceramide Trihexosides and Sulfatides, Random, Urine) may be elevated in patients with Fabry disease and can also be used in follow up of absent or reduced alpha-Gal A activity in both male and female patients.
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 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.
Molecular genetic testing is the recommended diagnostic test for female patients
Interpretation
In male patients, results less than 1.2 nmol/mL/hour in properly submitted specimens are consistent with Fabry disease. Normal results (≥1.2 nmol/mL/hour) are not consistent with Fabry disease.
In female patients, normal results (≥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, Varies) 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 activity but is not consistent with Fabry disease; FABRZ / Fabry Disease, Full Gene Analysis, Varies should be performed to resolve the clinical question.
For more information see Fabry Disease Diagnostic Testing Algorithm.
Clinical Reference
1. ACMG Newborn Screening ACT Sheets. Accessed October 30, 2023. 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 November 7, 2023. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225546984
3. Matern D, Gavrilov D, Oglesbee D, Raymond K, Rinaldo P, Tortorelli S. Newborn screening for lysosomal storage disorders. Semin Perinatol. 2015;39(3):206-216
4. Mehta A, Hughes DA: Fabry Disease. In: Pagon RA, Adam MP, Ardinger HH, et al: eds. GeneReviews [Internet]. University of Washington, Seattle; 2002. Updated March 9, 2023. Accessed November 7, 2023. Available at www.ncbi.nlm.nih.gov/books/NBK1292/
5. 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
Method Description
Whole blood is collected on grade 903 (Whatman) filter paper. A one-eighth inch (3-mm) disk is punched out of the dried blood spot into a 96-well plate. An elution liquid/inhibitor, N-acetyl-D-galactosamine, and 4-methylumbelliferyl-alpha-D-galactopyranoside in citrate-phosphate buffer as the substrate are added. After the incubation period, the liquid from the plate is manually transferred to a second 96-well plate. Stop buffer (150 mM EDTA) is added to all wells. A set of calibration standards are added to every plate and are derived from 4-methylumbelliferone (4-MU) that is serially diluted manually in the plate with the highest calibrator being equivalent to an enzyme activity of 12.2 nmol/mL/hour. The plate is then read on the spectrofluorometer. Fluorescence readings for duplicate wells are averaged and the average fluorescence is used to calculate the enzyme activity result.(Poeppl AG, Murray GJ, Medin JA. Enhanced filter paper enzyme assay for high-throughput population screening for Fabry disease. Anal Biochem. 2005;337(1):161-163; Cowan T, Pasquali M. Laboratory Investigations of Inborn Errors of Metabolism. In: Sarafoglou K, Hoffman GF, Roth KS eds. Pediatric Endocrinology and Inborn Errors of Metabolism. 2nd ed. McGraw-Hill; 2017:1139-1158)
Report Available
8 to 15 daysSpecimen Retention Time
1 yearReject Due To
| Shows serum rings Multiple layers | Reject |
Method Name
Fluorometric Enzyme Assay
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.
Cautions
Individuals with pseudodeficiency alleles can show reduced alpha-galactosidase A enzyme activity with this assay.