title: Pompe disease: Shared and unshared features of lysosomal storage disorders.
abstract: Pompe disease, an inherited deficiency of lysosomal acid α-glucosidase (GAA), is a severe metabolic myopathy with a wide range of clinical manifestations. It is the first recognized lysosomal storage disorder and the first neuromuscular disorder for which a therapy (enzyme replacement) has been approved. As GAA is the only enzyme that hydrolyses glycogen to glucose in the acidic environment of the lysosome, its deficiency leads to glycogen accumulation within and concomitant enlargement of this organelle. Since the introduction of the therapy, the overall understanding of the disease has progressed significantly, but the pathophysiology of muscle damage is still not fully understood. The emerging complex picture of the pathological cascade involves disturbance of calcium homeostasis, mitochondrial abnormalities, dysfunctional autophagy, accumulation of toxic undegradable materials, and accelerated production of lipofuscin deposits that are unrelated to aging. The relationship of Pompe disease to other lysosomal storage disorders and potential therapeutic interventions for Pompe disease are discussed.
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Health ; Bethesda, MD USA.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Lim
authors.affiliation: Department of Neurology; Hadassah-Hebrew University Medical Center ; Ein Kerem, Jerusalem, Israel.
authors.forename: Or
authors.initials: O
authors.lastname: Kakhlon
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Health ; Bethesda, MD USA.
authors.forename: Lishu
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Health ; Bethesda, MD USA ; St. Mary's College of Maryland ; St. Mary's City, MD USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Myerowitz
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Health ; Bethesda, MD USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Raben
keywords: Pompe disease; autophagy; calcium; lysosomal storage diseases; lysosome; mitochondria