Pompe disease (Glycogen storage disease type II;MIM 232300) is a classical lysosomal storage disorder that causes death in the first year of life for patients with the infantile form due to a progressive cardiomyopathy leading to cardiorespiratory failure. Myozyme (alglucosidase alpha, recombinant human acid alpha-glucosidase/GAA, rhGAA) was approved in April 2006 as a treatment for Pompe Disease. The availability of ERT with Myozyme has improved the outcome of most patients with Pompe disease;however, a subset of infantile Pompe patients responds poorly to ERT, subsequently dying from cardiorespiratory failure. Poorly-responding Pompe disease patients generally lack residual GAA expression and these patients are cross-reacting immune material-negative (CRIM-negative).
The Aims of this proposal would evaluate these rare CRIM-negative Pompe disease patients on ERT +/- immune suppression, by enrolling them in a prospective/retrospective natural history study through the Lysosomal Disease Network. Subjects would be enrolled from the Network and data collected regarding a number of clinical endpoints to determine the natural history of this disorder. Enrollment will include patients for whom a poor clinical response to current therapy is predicted. Patients studied will be all infantile crossreacting immune material (CRIM)-negative Pompe disease patients on a clinical protocol starting enzyme replacement therapy (ERT) with or without immune suppression. They will be compared to data obtained from infantile CRIM-positive Pompe disease patients started on ERT at similar ages and also enrolled in the protocol monitoring history and outcome of the disease on ERT.

Public Health Relevance

A poor response to therapy is predicted for infants who are CRIM-negative;we will study their natural history compared to those who respond well to ERT and determine whether immune suppression is beneficial.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZRG1-HOP-Y (50))
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University of Minnesota Twin Cities
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