Test Catalog

Test Id : PDCRF

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Pompe Disease Cross-Reactive Immunological Material Status, Fibroblasts

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Overview

Test Catalog

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

Determination of cross-reactive immunologic material status in patients with Pompe disease

 

Evaluating the best strategy for enzyme replacement therapy for patients with Pompe disease

Highlights

This test is used to determine cross-reactive immunological material (CRIM) status in patients with Pompe disease.

 

CRIM status is important when assessing whether immunosuppression is needed when initiating enzyme replacement therapy for patients with Pompe disease.

Additional Tests
Lists tests that are always performed, at an additional charge, with the initial tests.

Test Id Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes Yes

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, fibroblast culture testing will always be performed at an additional charge. If viable cells are not obtained, the client will be notified. 

 

For more information see Newborn Screen Follow-up for Pompe Disease.

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

PDCRF: Western blot

CULFB: Cell Culture

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

Pompe Disease CRIM Status, Fibro

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

CRIM

Cross-reactive immunological material

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, fibroblast culture testing will always be performed at an additional charge. If viable cells are not obtained, the client will be notified. 

 

For more information see Newborn Screen Follow-up for Pompe Disease.

Specimen Type
Describes the specimen type validated for testing

Tissue

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

Submit only 1 of the following specimens:

 

Specimen Type: Cultured fibroblasts

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

Specimen Volume: 1 Full T-75 flask 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

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

Forms

1. Biochemical Genetics Patient Information (T602)

2.  If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

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

Specimen in formalin or fixative preservative  Reject

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
Tissue Varies

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

Determination of cross-reactive immunologic material status in patients with Pompe disease

 

Evaluating the best strategy for enzyme replacement therapy for patients with Pompe disease

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, fibroblast culture testing will always be performed at an additional charge. If viable cells are not obtained, the client will be notified. 

 

For more information see Newborn Screen Follow-up for Pompe Disease.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA; acid maltase) due to alterations in the GAA gene. The estimated incidence is 1 in 40,000 live births. In Pompe disease, glycogen is taken up by lysosomes during physiologic cell turnover and accumulates, causing lysosomal swelling and cell damage, which results in organ dysfunction. Symptoms include progressive muscle weakness, cardiomyopathy, and, eventually, death if untreated.

 

Clinically, Pompe disease 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 variant and is characterized by early onset and rapid progression of cardiac, liver, and muscle problems resulting in death within the first year of life. The infantile variant of Pompe disease has a similar age of onset but a milder clinical presentation. Late-onset Pompe disease can present with muscle weakness, cardiomyopathy, and/or respiratory dysfunction in childhood or later, including advanced adulthood. The rate of progression and severity of symptoms is variable, particularly in the late-onset forms.

 

Treatment with enzyme replacement therapy (ERT) is available, making early diagnosis of Pompe disease desirable because early initiation of treatment improves the prognosis. Treatment with ERT can prolong survival in patients with infantile onset Pompe disease; however, the effectiveness of treatment is impacted by the presence or absence of cross-reactive immunologic material (CRIM) to the GAA enzyme. Patients who are CRIM-negative are more likely to develop antibodies against recombinant human GAA than patients who are CRIM-positive, thereby decreasing the effectiveness of treatment. Strategies to decrease the immune response to ERT, such as immunosuppression, rely on determination of CRIM status.

 

Molecular analysis of the GAA gene can determine CRIM status in over 90% of patients with Pompe disease (GAAZ / Pompe Disease, Full Gene Analysis, Varies). However, for those who have GAA variants not classified as either CRIM-negative or -positive, CRIM testing in fibroblasts or leukocytes can determine final CRIM status. Therefore, CRIM testing is useful for either confirmation of CRIM status determined by molecular testing or determination of CRIM status if the genotype is not informative.

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

The presence of cross-reactive immunologic material (CRIM) indicates a decreased likelihood that a patient affected with Pompe disease (acid alpha-glucosidase: GAA deficiency) will develop an immune response to enzyme replacement therapy with recombinant GAA.

 

The absence of CRIM in untreated patients with Pompe disease indicates a need to consider additional measures to prevent an immune response to the administration of enzyme replacement therapy with recombinant GAA.

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

The test by itself is not diagnostic of Pompe disease, and results need to be interpreted in light of the clinical presentation and other laboratory tests, such as creatine kinase, acid alpha-glucosidase (GAA) activity, and GAA genotype.

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

1. Kishnani PS, Goldenberg PC, DeArmey SL, et al: Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants. Mol Genet Metab. 2010 Jan;99(1):26-33

2. Bali DS, Goldstein JL, Rehder C, et al: Clinical laboratory experience of blood CRIM testing in infantile Pompe disease. Mol Genet Metab Rep. 2015 Dec 1;5:76-79. doi: 10.1016/j.ymgmr.2015.10.012

3. Reuser AJ, Hirschhorn R, Kroos MA: Pompe disease: Glycogen storage disease type II, acid alpha-glucosidase (acid maltase) deficiency. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed October 11, 2022. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225890450

4. Leslie N, Bailey L: Pompe disease. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet].  University of Washington, Seattle; 2007. Updated May 11, 2017. Accessed October 11, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1261/

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

Western blot analysis is performed using fibroblasts cultured from a skin biopsy. Lysed cells are quantitated for protein, separated by gel electrophoresis, and transferred to a polyvinylidene difluoride (PVDF) membrane. The PVDF membrane is then incubated with antibodies specific to acid alpha-glucosidase (GAA, the protein of interest) and b-actin (used as an internal quality control protein). A chemiluminescent substrate is added to the membrane and the emitted light signal is captured by digital imaging. If specific bands are present, the patient is determined to be cross-reactive immunologic material (CRIM)-positive while the absence of these bands indicates a CRIM-negative result.(Wang Z, Okamoto P, Keutzer J: A new assay for fast, reliable CRIM status determination in infantile-onset Pompe disease. Mol Genet Metab. 2014 Feb;111[2]:92-100)

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.

30 to 45 days

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

6 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.

84182-Pompe CRIM

88233-Fibroblast culture

88240-Cryopreservation for biochemical studies

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
PDCRF Pompe Disease CRIM Status, Fibro 99309-7
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
606123 GAA CRIM status In Process
606124 Interpretation 59462-2
606125 Reviewed By 18771-6

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