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Test ID: AGABS Alpha-Galactosidase, Blood Spot

Reporting Name

Alpha-Galactosidase, BS

Useful For

Evaluation of 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 Testing Algorithm

-Fabry Disease: Newborn Screen-Positive Follow-up

Specimen Type

Whole blood


Additional Testing Requirements


Additional studies including molecular genetic analysis of the GLA gene (FABRZ / Fabry Disease, Full Gene Analysis) 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 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 (T493)

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 in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

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


Specimen Minimum Volume

1 blood spot

Specimen Stability Information

Specimen Type Temperature Time
Whole blood Ambient (preferred) 90 days
  Frozen  90 days
  Refrigerated  90 days

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

Set up Wednesday, report Thursday; morning

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 In Process
50893 Release Date 82772-5

Clinical Information

Fabry disease is an X-linked recessive lysosomal storage disorder resulting from deficient activity of the enzyme alpha-galactosidase A (a-Gal A) and the subsequent deposition of glycosylsphingolipids in tissues throughout the body, in particular, the kidney, heart, and brain. More than 150 mutations in the GLA gene have been identified in individuals diagnosed with Fabry disease. Severity and onset of symptoms are dependent on the amount of residual enzyme activity. The classic form of Fabry disease occurs in males who have less than 1% a-Gal A activity. Symptoms usually appear in childhood or adolescence and can include acroparesthesias (pain crises in the extremities), multiple angiokeratomas, reduced or absent sweating, and corneal opacity. In addition, progressive renal involvement leading to end-stage renal disease typically occurs in adulthood followed by cardiovascular and cerebrovascular disease. The estimated incidence is 1 in 40,000 males.

 

Males with residual a-Gal A activity above 1% may present with 1 of 3 variant forms of Fabry disease with onset of symptoms later in life. These include a renal variant associated with end stage renal disease (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.

 

Unless irreversible damage has already occurred, treatment with enzyme replacement therapy (ERT) has led to significant clinical improvement in affected individuals. 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.

 

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 have normal levels of alpha-Gal A. Additional studies including molecular genetic analysis of the GLA gene (FABRZ / Fabry Disease, Full Gene Analysis) are recommended to detect carriers.

 

Reduced or absent a-Gal A in blood spots, 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) allows for detection of the disease-causing mutation.

 

The following algorithms are available in Special Instructions:

-Fabry Disease Testing Algorithm

-Fabry Disease: Newborn Screen-Positive Follow-up

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) 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 should be performed to resolve the clinical question.

    

See Fabry Disease 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;308:195-196

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. Spada M, Pagliardini S, Yasuda M, et al: High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet 2006;79:31-40

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

5. Mehta A, Hughes DA: Fabry disease. In GeneReviews Accessed 1/23/2017. Available at www.ncbi.nlm.nih.gov/books/NBK1292/

Analytic Time

8 days

Method Name

Fluorometric Enzyme Assay

Forms

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

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

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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