This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Pompe disease is a rare autosomal recessive disease caused by the deficiency of acid alpha-glucosidase (GAA), which is needed for the degradation of lysosomal glycogen. Other names for Pompe disease include glycogen storage disease type I1 (GSD-1 l), acid maltase deficiency (AMD) and glycogenosis type 11. Pompe disease is characterized by organelle bound (lysosomal) accumulation of glycogen in many body tissues, as opposed to the exclusive cytoplasmic accumulation of glycogen that occurs in most other glycogen storage disorders.Clinical presentation of GAA deficiency ranges from a rapidly fatal infantile disease to a slowly progressive late-onset myopathy frequently associated with respiratory insufficiency. In general, there is an inverse correlation between the amount of residual GAA activity and the severity of the disease, i.e., the higher the activity the less severe the disease.The incidence of Pompe disease appears to vary in different ethnic groups. Estimates of the frequency of infantile-onset Pompe disease in the Caucasian population range from 1: 100,000 to 1 :200,000. The calculated incidence of all Pompe disease phenotypes is estimated to be 1:40,000. The incidence of infantile-onset Pompe disease may be the highest among Blacks (estimated 1:14,000) and among Chinese (estimated 1:40,000 to 1 :50,000).There is currently no approved, effective treatment for Pompe disease. Palliative and supportive care provides the mainstay of management. Enzyme replacement therapy may be effective in slowing or reversing symptoms of the disease or converting a more severe phenotype into a milder phenotype.Genzyme has developed recombinant human acid alpha-glucosidase (rhGAA) (MyozymeTM) as enzyme replacement therapy for the treatment of Pompe disease. It is hoped that enzyme replacement therapy will restore enzymatic activity, deplete accumulated substrate, and prevent further accumulation.The overall objective of this study is to evaluate the long-term safety and efficacy of Myozyme treatment in patients with infantile-onset Pompe disease. The primary objective of the study is to determine the proportion of patients treated with Myozyme (20 mgkg dose group, 40 mgkg dose group, and both dose groups combined) who are alive and free of invasive ventilatory support after each 52 week Maintenance Phase Module and at the end of the study which will be estimated using the Kaplan-Meier methodology.
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