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Test ID AGABS Alpha-Galactosidase, Blood Spot

Reporting Name

Alpha-Galactosidase, BS

Useful 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

Testing Algorithm

The following algorithms are available in Special Instructions:

-Fabry Disease Diagnostic Testing Algorithm

-Fabry Disease: Newborn Screen-Positive Follow-up

 

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

Specimen Type

Whole blood


Advisory Information


This test is not suitable for carrier detection in females. It is recommended that molecular testing (FABRZ / Fabry Disease, Full Gene Analysis, Varies) be performed for diagnosis in females.



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.

 

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



Necessary Information


Provide a reason for referral with each specimen.



Specimen Required


Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Container/Tube:

Preferred: Blood spot collection card

Acceptable: 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 >1 year of age is fingerstick.

3. Let blood dry on the filter paper at ambient temperature in a horizontal position for 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 in Special Instructions.

2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.


Specimen Minimum Volume

Blood spot: 1

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

Reference Values

Males: ≥1.2 nmol/mL/hour

Females: ≥2.8 nmol/mL/hour

An interpretive report will be provided.

Day(s) and Time(s) Performed

Varies

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

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 49549-9
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 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.

 

Measurement of alpha-Gal A in blood spots, leukocytes (AGA / 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 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. 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.

 

Females 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 (CTSA / Ceramide Trihexosides and Sulfatides, 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 males and females.

 

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.

 

Molecular genetic testing is the recommended diagnostic test for females as alpha-Gal A may be in the normal range in an affected female patient.

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, but is not consistent with Fabry disease; FABRZ / Fabry Disease, Full Gene Analysis, Varies should be performed to resolve the clinical question.

 

See Fabry Disease Diagnostic Testing Algorithm in Special Instructions.

Clinical Reference

1. Chamoles NA, Blanco M, Gaggioli D: Fabry disease: enzymatic diagnosis in dried blood spots on filter paper. Clin Chim Acta 2001 Jun;308(1-2):195-196

2. 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, McGraw-Hill. Accessed 2/14/2019.Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225546984&bookid=2709&Resultclick=2

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

4. Mehta A, Hughes DA: Fabry Disease. In GeneReviews. Updated 5 Jan 2017.Edited by RA Pagon, MP Adam, HH Ardinger, et al. University of Washington, Seattle, Accessed 2/11/2019. 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 Oct;22(5):555-564

Analytic Time

8 days

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 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 | Pediatric Catalog Additional Information:

mcl-newborn