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Test ID: GAAZ Pompe Disease, Full Gene Analysis, Varies

Reporting Name

Pompe Disease Full Gene Analysis

Useful For

Confirmation of diagnosis of Pompe disease (as a follow-up to biochemical analyses)

Clinical Information

Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive condition caused by deficiency of acid alpha-glucosidase. Enzyme insufficiency results in symptoms such as muscle weakness, cardiomyopathy, and respiratory problems. Pathogenic alterations in the GAA gene (which encodes acid alpha-glucosidase) are associated with Pompe disease.

 

The diagnosis of this heterogeneous condition relies on both clinical and laboratory evaluation. Clinically, the condition is categorized into infantile and late-onset forms based on age of onset, organ involvement, and rate of progression. The infantile form (or classic Pompe disease) is the most severe form and is characterized by early onset and rapid progression of cardiac, liver, and muscle problems resulting in death within the first year. The infantile variant form has a similar age of onset but a milder clinical presentation. On the less severe end of the spectrum is the late-onset form with childhood, juvenile, or adult onset. The rate of progression and severity of symptoms is quite variable, particularly in the late-onset forms. The incidence varies by clinical type and ethnic population; the combined incidence is approximately 1 in 40,000 individuals.

 

The calculated ratio of creatine (Cre) and creatinine (Crn) to acid-alpha glucosidase (GAA) activity is useful for individuals with a suspected diagnosis of Pompe disease; for patients older than 6 weeks, order PDBS / Pompe Disease, Blood Spot; for patients 6 weeks and younger, order PD2T / Pompe Disease Second-Tier Newborn Screening, Blood Spot. Alternatively, enzyme studies can be ordered on blood via GAAW / Acid Alpha-Glucosidase, Leukocytes. When clinical manifestations and results of that analysis are supportive of a diagnosis of Pompe disease, variant analysis of the GAA gene is warranted. Additionally, measurement of the urine glucotetrasaccharide biomarker can aid in diagnosis and ongoing therapeutic monitoring (HEX4 / Glucotetrasaccharides, Random, Urine)

 

Over 250 different variants have been identified in this gene including point alterations and large deletions. GAA full gene sequencing provided by this test will detect 2 variants in approximately 83% to 93% of individuals with confirmed GAA enzyme deficiency. Identification of genetic variants provides confirmation of the diagnosis and allows for subsequent testing of at risk family members.

Interpretation

All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
FIBR Fibroblast Culture Yes No
CRYOB Cryopreserve for Biochem Studies No No

Testing Algorithm

If skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be performed at an additional charge.

 

See the following in Special Instructions.

-Newborn Screen Follow-up for Pompe Disease 

-Newborn Screening Act Sheet Pompe Disease: Decreased Acid Alpha-Glucosidase

Analytic Time

14 days

Day(s) and Time(s) Performed

Performed weekly; Varies

Clinical Reference

1. 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

2. Kishnani PS, Steiner RD, Bali D, et al: Pompe disease diagnosis and management guideline. Genet Med. 2006 May;8(5):267-288

3. Van der Ploeg AT, Reuser AJJ: Pompe's disease. Lancet. 2008;372(9646):1342-1353

4. Kroos M, Pomponio RJ, van Vliet L, et al: Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. Hum Mut. 2008;29(6):E13-26

5. Reuser AJJ, Hirschhorn R, Kroos MA: Pompe disease: Glycogen storage disease type II, acid a-glucosidase (acid maltase) deficiency. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed June 30, 2020. Available at: https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225890450

Method Name

Polymerase Chain Reaction (PCR) followed by DNA Sequencing

Specimen Type

Varies


Advisory Information


For first tier testing for individuals older than 6 weeks with a suspected diagnosis of Pompe disease, order PDBS / Pompe Disease, Blood Spot. If the patient is 6 weeks old or younger, order PD2T / Pompe Disease Second-Tier Newborn Screening, Blood Spot.

 

Alternatively, enzyme studies can be performed on whole blood; order GAAW / Acid Alpha-Glucosidase, Leukocytes.

 

For measurement of ongoing therapeutic monitoring, order HEX4 / Glucotetrasaccharides, Random, Urine.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Specimen Required


Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1740 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) or yellow top (ACD)

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

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated 24 hours

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115])

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

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.


Specimen Minimum Volume

Blood: 1 mL
Blood Spots: 5 punches-3 mm diameter

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reference Values

An interpretive report will be provided.

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

81406-GAA (glucosidase, alpha; acid) (eg, glycogen storage disease type II [Pompe disease]), full gene sequence

88233-Tissue culture, skin or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GAAZ Pompe Disease Full Gene Analysis 76034-8

 

Result ID Test Result Name Result LOINC Value
53915 Result Summary 50397-9
53916 Result 82939-0
53917 Interpretation 69047-9
53918 Additional Information 48767-8
53919 Specimen 31208-2
53920 Source 31208-2
53921 Released By 18771-6

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: Congenital Inherited Diseases Patient Information (T521) in Special Instructions

3. If not ordering electronically, complete, print, and send an Inborn Errors of Metabolism Test Request (T798) with the specimen.