Determination of CRIM Status and Longitudinal Follow-up of Individuals With Pompe Disease

Infantile-onset Pompe disease is an inherited disorder caused by lack of or defect in the
enzyme acid alpha-glucosidase (GAA). GAA enzyme deficiency causes glycogen to build up and
damage cells throughout the body, especially in the heart and muscles, which is normally
diagnosed within the first months of life. Current treatment for Pompe disease involves
enzyme replacement therapy (ERT) using the drug alglucosidase alfa (Myozyme), which provides
a form of the GAA enzyme to replace the enzyme that is missing or not working properly in the
patient's blood.

In this study, the investigators will learn about the patient's ability to tolerate ERT.
Cross-Reactive Immunological Material (CRIM) is a measurement of natural GAA production and
an important factor that affects how patients respond to ERT with Myozyme. Children who
produce some natural GAA are classified as CRIM positive (+), while children who do not
produce any natural GAA are classified as CRIM negative (-). Children who are CRIM+ generally
tolerate ERT well. But, children who are CRIM-, and some children classified as CRIM+, have a
poor response to ERT due to complications from an immune response against the drug.
Treatments are currently being developed to stop this immune response and prevent
complications from ERT.

This is a longitudinal natural history study of Infantile Pompe disease. The investigators
will regularly collect and review medical information for up to 10 years regarding the
diagnosis of Pompe disease, response to enzyme replacement (ERT) using alglucosidase alfa
(Myozyme) and response to immunosuppressive therapy in cases at risk for developing or those
who have developed high and sustained antibodies to ERT. A subset of de-identified
information about the natural history of Pompe disease and the response to treatment will be
incorporated into the Lysosomal Disease Network (LDN) disease registry. The LDN is a
nonprofit organization of scientists located around the world whose research focuses on
Lysosomal disease.

The specific aims of this study are:

1. To determine and correlate Cross-Reactive Immunological Material (CRIM) status with the
GAA gene mutations found on these patients

2. To validate an approach for determining CRIM status from whole blood sample, with the
gold standard determination of CRIM status by skin fibroblasts and mutation analysis

3. To explore the clinical treatment response and natural history of CRIM-positive and
CRIM-negative Pompe disease patients with and without immune modulation

4. To investigate the role of immune response to treatment

Inclusion Criteria:

- Confirmed diagnosis of infantile, atypical or juvenile onset Pompe disease

- Must have a parent or guardian provide written informed consent

Exclusion Criteria:

- Age 18 or older