Long-term Follow-up of Response to Treatment and Immune Tolerance Induction (ITI) in Pompe Disease

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 understand the developing natural history of Pompe disease, in both treated and untreated patients;
2. To evaluate the success of Immune Tolerance Induction (ITI) for CRIM- patients and CRIM+ patients who develop high and sustained antibodies to ERT.
3. To share the natural history of the disease progress and response to treatment information with scientists around the world who are investigating Pompe disease and other Lysosomal diseases.

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 understand the developing natural history of Pompe disease, in both treated and untreated patients;
2. To evaluate the success of Immune Tolerance Induction (ITI) for CRIM- patients and CRIM+ patients who develop high and sustained antibodies to ERT.
3. To share the natural history of the disease progress and response to treatment information with scientists around the world who are investigating Pompe disease and other Lysosomal diseases.

Study subjects will be babies/children with a confirmed diagnosis of infantile-onset Pompe disease who are:

1. seen by the clinical staff of Duke Division of Medical Genetics, or
2. whose physician or parent contacts the Duke Division of Medical Genetics with the wish to participate in this CRIM research study.

• El-Gharbawy AH, Mackey J, DeArmey S, Westby G, Grinnell SG, Malovrh P, Conway R, Kishnani PS. An individually, modified approach to desensitize infants and young children with Pompe disease, and significant reactions to alglucosidase alfa infusions. Mol Genet Metab. 2011 Sep-Oct;104(1-2):118-22. Epub 2011 Jul 13.
• Banugaria SG, Prater SN, Ng YK, Kobori JA, Finkel RS, Ladda RL, Chen YT, Rosenberg AS, Kishnani PS. The impact of antibodies on clinical outcomes in diseases treated with therapeutic protein: lessons learned from infantile Pompe disease. Genet Med. 2011 Aug;13(8):729-36.
• Messinger YH, Mendelsohn NJ, Rhead W, Dimmock D, Hershkovitz E, Champion M, Jones SA, Olson R, White A, Wells C, Bali D, Case LE, Young SP, Rosenberg AS, Kishnani PS. Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease. Genet Med. 2012 Jan;14(1):135-42. doi: 10.1038/gim.2011.4.
• Mendelsohn NJ, Messinger YH, Rosenberg AS, Kishnani PS. Elimination of antibodies to recombinant enzyme in Pompe's disease. N Engl J Med. 2009 Jan 8;360(2):194-5.

Inclusion Criteria:

• Confirmed diagnosis of Infantile Pompe disease
• Must have a parent or guardian provide written informed consent

Exclusion Criteria:

• Age 12 or older