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Test ID: PDCRF Pompe Disease Cross-Reactive Immunological Material Status, Fibroblasts

Specimen Required

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


1. Biochemical Genetics Patient Information (T602)

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

Useful For

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

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.

Method Name

PDCRF: Western blot

CULFB: Cell Culture

Reporting Name

Pompe Disease CRIM Status, Fibro

Specimen Type


Specimen Stability Information

Specimen Type Temperature Time Special Container
Tissue Varies

Clinical Information

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

An interpretive report will be provided


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.

Clinical Reference

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

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

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 US Food and Drug Administration.

CPT Code Information

84182-Pompe CRIM

88233-Fibroblast culture

88240-Cryopreservation for biochemical studies

LOINC Code Information

Test ID Test Order Name Order LOINC Value
PDCRF Pompe Disease CRIM Status, Fibro 99309-7


Result ID Test Result Name Result LOINC Value
606123 GAA CRIM status In Process
606124 Interpretation 59462-2
606125 Reviewed By 18771-6

Day(s) Performed


Report Available

30 to 45 days

Additional Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes Yes
Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information: