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

Study Overview
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Brief Summary
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This is a longitudinal natural history study of Infantile Pompe disease. The investigators will regularly collect and review medical information regarding the diagnosis of Pompe disease, response to enzyme replacement (ERT) using alglucosidase alfa (Lumizyme/Myozyme) and response to immunosuppressive therapy in cases at risk for developing or those who have developed high and sustained antibodies to ERT. To follow the long-term outcomes, we will collect medical records including but not limited to the diagnosis, clinical parameters, assessments for clinical monitoring, and laboratory values including antibody testing results.

Detailed Description
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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 (Lumizyme/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. 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-positive generally tolerate ERT well. But, children who are CRIM-negative, and some children classified as CRIM-positive, 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 regarding the diagnosis of Pompe disease, response to enzyme replacement (ERT) using alglucosidase alfa (Lumizyme/Myozyme) and response to immunosuppressive therapy in cases at risk for developing or those who have developed high and sustained antibodies to ERT. The specific aims of this study are: To correlate CRIM status determined in a blood sample or cultured skin fibroblasts with GAA gene variants that are causing your child's Pompe disease. To explore the clinical treatment response and natural history of CRIM-positive and CRIM-negative Pompe disease patients with and without immune modulation. To investigate the role of immune response to treatment (IgG and IgE) including immune phenotyping.

Official Title
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Determination of Cross-Reactive Immunological Material (CRIM) Status and Longitudinal Follow-up of Individuals With Pompe Disease

Conditions
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Pompe Disease

Intervention / Treatment
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* Other: Observational


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of infantile, atypical or juvenile onset Pompe disease Must have a parent or guardian provide written informed consent

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Infantile Pompe disease<br>Individuals with a confirmed diagnosis of Infantile Pompe disease | Other: Observational<br>* This is a longitudinal study focused on the emerging natural history of Infantile Pompe disease, response to ERT using alglucosidase alfa (Myozyme) and response to Immune Tolerance Induction (ITI).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response to enzyme replacement therapy (ERT) using alglucosidase alfa (Myozyme) | Medical records will be tracked until the patient reaches the age of 18 years to follow clinical response to ERT. This will allow us to gain an understanding of CRIM status in relation to clinical outcomes and development for these subjects. | Up to 18 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to Immune Tolerance Induction (ITI) | Medical records will be tracked until the patient reaches the age of 18 years to follow clinical response to Immune Tolerance Induction (ITI) for patients who are CRIM- or CRIM+ with high antibody titers. This will allow us to increase our understanding of the history of Pompe disease in relation to treatment interventions and the role of high antibody titers in terms of patient outcome in order to develop strategies to ameliorate the immune response and other factors that may affect response to ERT. | Up to 18 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pompe disease, Glycogen Storage Disease Type II, Acid Maltase Deficiency, CRIM Status, Acid Alpha-Glucosidase Deficiency, Alglucosidase alfa, Myozyme, Enzyme replacement therapy, Immune Tolerance Induction, Lumizyme, Immunomodulation, Anti-drug antibodies