AGLU03206 OPEN LABEL EXTENSION OF AGLU02704

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pompe disease is a rare autosomal recessive metabolic muscle disease caused by the deficiency of acid Q glucosidase an enzyme that degrades lysosomal glycogen. As opposed to the exclusively cytoplasmic accumulation of glycogen that occurs in other glycogen storage disorders, Pompe disease is characterized by organelle bound lysosomal and extra-lysosomal accumulation of glycogen in many body tissues, ultimately leading to multisystemic pathology. Pompe disease is classified into different subtypes based on the age at onset of symptoms, extent of organ involvement, and rate of progression to death. There is a broad spectrum of disease ranging from a rapidly progressive form infantile-onset to a more slowly progressive form late-onset with considerable variability and overlap existing between these extremes. It is important to note that all presentations of Pompe disease share a common underlying pathology; i.e., deficiency of GAA with subsequent accumulation of glycogen. Symptoms appear during childhood or as late as the sixth decade of life. Patients present with progressive myopathy, predominantly of the proximal muscles in the pelvic and shoulder girdles, and a variable progression of respiratory involvement. The patients develop minimal or no cardiomyopathy. The course of late-onset Pompe disease is less predictable than the infantile form, with some patients experiencing a rapid deterioration in skeletal and respiratory muscle function leading to loss of ambulation and respiratory failure, others progressing less rapidly, and others with dissociation in the progression of skeletal and respiratory muscle involvement . Most patients become wheelchair-bound, require ventilator support and ultimately succumb to respiratory failure.