Test Catalog

Test Id : FABRZ

Fabry Disease, Full Gene Analysis, Varies

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

Confirmation of a diagnosis of classic or variant Fabry disease in affected males with reduced alpha- galactosidase A enzyme activity

 

Carrier or diagnostic testing for asymptomatic or symptomatic females, respectively

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.

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

Method Name
A short description of the method used to perform the test

Polymerase Chain Reaction (PCR) followed by DNA Sequencing

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Fabry Disease Full Gene Analysis

Aliases
Lists additional common names for a test, as an aid in searching

Alpha-Galactosidase A

Anderson-Fabry Disease

Cardiac Variant Fabry Disease

Renal Variant Fabry Disease

FABMS

GLA

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.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

The recommended first-tier test for males with suspected Fabry disease is alpha-galactosidase A enzyme activity in blood or serum. Order either AGAW / Alpha-galactosidase, Leukocytes or AGAS / Alpha-galactosidase, Serum.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Submit only 1 of the following specimens:

 

Preferred:

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) tube or yellow top (ACD) tube

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Acceptable:

Specimen Type: Blood spot

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

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: Ahlstrom 226 filter paper, or Blood Spot Collection Card

Specimen Volume: 2 to 5 Blood spots on collection card

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year of age is finger stick.

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

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry.

Specimen Stability Information: Ambient (preferred)/Refrigerated

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.

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

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. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 1 mL

Blood Spots: 5 punches-3 mm diameter

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

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

Confirmation of a diagnosis of classic or variant Fabry disease in affected males with reduced alpha- galactosidase A enzyme activity

 

Carrier or diagnostic testing for asymptomatic or symptomatic females, respectively

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 recessive disorder with an incidence of approximately 1 in 50,000 males. Symptoms result from a deficiency of the enzyme alpha-galactosidase A (alpha-Gal A). Reduced alpha-Gal A activity results in accumulation of glycosphingolipids in the lysosomes of both peripheral and visceral tissues.

 

Severity and onset of symptoms are dependent on the residual alpha-Gal A activity. Males with less than 1% alpha-Gal A activity have the classic form of Fabry disease. Symptoms can appear in childhood or adolescence and usually include acroparesthesias (pain crises), multiple angiokeratomas, reduced or absent sweating, and corneal opacity. By middle age, most patients develop renal insufficiency leading to end-stage renal disease, as well as cardiac and cerebrovascular disease. Males with greater than 1% alpha-Gal A activity may present with a variant form of Fabry disease. The renal variant generally has onset of symptoms in the third decade. The most prominent feature in this form is renal insufficiency and, ultimately, end-stage renal disease. Individuals with the renal variant may or may not have other symptoms of classic Fabry disease. Individuals with the cardiac variant are often asymptomatic until they present with cardiac findings such as cardiomyopathy or mitral insufficiency later in life. The cardiac variant is not associated with renal failure.

 

Female carriers of Fabry disease can have clinical presentations ranging from asymptomatic to severe. 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.

 

Alterations in the GLA gene result in deficiency of alpha-Gal A. Most of the alterations identified to date are family specific. Full sequencing of the GLA gene identifies over 98% of the sequence variants in the coding region and splice junctions. In addition, this assay detects the intron 4 alteration common in the Taiwanese population.(1)

 

The recommended first-tier test for males with suspected Fabry disease is biochemical testing that measures alpha-galactosidase enzyme activity in blood or serum: AGAW / Alpha-galactosidase, Leukocytes or AGAS / Alpha-galactosidase, Serum. Additionally, testing for the glycosphingolipid, globotriaosylsphingosine (LGb3) may aid in further clarifying disease status in both males and females with suspected Fabry disease (LGB3 / Globotriaosylsphingosine, Serum). Individuals with decreased or absent enzyme activity and elevated LGb3 are more likely to have an identifiable alterations in the GLA gene by molecular genetic testing. However, enzymatic testing alone is not reliable to detect female carriers.

 

The following algorithms are available in Special Instructions:

-Fabry Disease: Newborn Screen-Positive Follow-up algorithm

-Fabry Disease Diagnostic Testing Algorithm

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.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

All detected alterations will be evaluated according to the American College of Medical Genetics and Genomics (AMCG) recommendations.(2) Variants will be classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

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

A small percentage of individuals who are carriers or have a diagnosis of Fabry disease may have a variant that is not identified by this method (eg, large genomic deletions, promoter alterations). The absence of a variant, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of Fabry disease. For carrier testing, it is important to first document the presence of a GLA gene variant in an affected family member.

 

In some cases, DNA alterations of undetermined significance may be identified.

 

Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical and biochemical findings, additional testing should be considered.

  

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

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

1. Hwu WL, Chien YH, Lee NC, et al: Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>A). Hum Mutat. 2009:30(10):1397-1405

2. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424

3. Germain DP: Fabry disease. Orphanet J Rare Dis. 2010 Nov 22;5:30

4 Wang RY, Lelis A, Mirocha J, Wilcox WR: Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med. 2007 Jan;9(1):34-35

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

Method Description
Describes how the test is performed and provides a method-specific reference

Bidirectional sequence analysis is performed to test for the presence of a sequence variant in all coding regions and intron/exon boundaries of the GLA gene.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

14 to 20 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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 US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81405-GLA (galactosidase, alpha) (eg, Fabry disease), full gene sequence

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports