Gene therapy for Pompe disease with adeno-associated virus (AAV) vectors has advanced into early phase clinical trials; however, the paucity of cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle, where it is needed to take up acid α-glucosidase (GAA), has impeded the efficacy of Pompe disease gene therapy.
Glycogen storage disease II (GSDII), also called Pompe disease, is an autosomal recessive inherited disease caused by a defect in glycogen metabolism due to the deficiency of the enzyme acid alpha-glucosidase (GAA) responsible for its degradation.
Regulation of α-glucosidase (EC 3.2.1.20) and its inhibitors is of great interest to researchers due to its clinical relevance as a target enzyme for the treatment of α-glucosidase-mediated diseases, such as type 2 diabetes mellitus and Pompe disease.
Recombinant human acid α-glucosidase (Myozyme) is the only drug approved by the United States Food and Drug Administration for the treatment of Pompe disease.
Neonatal screening for Pompe disease is complicated by difficulties in predicting symptom onset in patients with the common c.-32-13T>G (IVS1) variant/null (i.e. fully deleterious) acid α-glucosidase (GAA) genotype.
We present a computational model for predicting mutational impact on enzymatic activity of human acid α-glucosidase (GAA), an enzyme associated with Pompe disease.
Thus, it was difficult to distinguish newborns with c.[1726G>A; 2965G>A] alleles from newborns with pre-symptomatic Pompe disease using AαGlu assays in DBSs or fibroblasts; GAA gene sequencing was necessary.
Late-onset Pompe disease (LOPD) is a recessive disease caused by α-glucosidase (GAA) deficiency, leading to progressive muscle weakness and/or respiratory failure in children and adults.
Pompe disease (PD) is an autosomal recessive lysosomal disorder caused by the deficient activity of acid alpha-glucosidase (GAA) enzyme due to mutations in the <i>GAA</i> gene.
We performed genetic analysis to confirm the diagnosis of Pompe disease in a 61-year-old patient with progressive weakness in extremities, severe Sleep Apnea-Hypopnea Syndrome, a significant reduction of alpha-glucosidase in liquid sample of peripheral blood and muscular biopsy diagnosis.
Pompe disease is a neuromuscular disease caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase leading to lysosomal and cytoplasmic glycogen accumulation in neurons and striated muscle.
Pompe disease is an autosomal recessive lysosomal storage disease caused by acid α-glucosidase (GAA) deficiency, resulting in intralysosomal accumulation of glycogen, including cardiac, skeletal, and smooth muscle cells.
For example, glucose-6-phosphatase (G6Pase) deficiency in GSD type Ia (GSD Ia) affects primarily the liver and kidney, while acid α-glucosidase (GAA) deficiency in GSD II causes primarily muscle disease.
Pompe disease (PD) is caused by the deficiency of the lysosomal enzyme acid α-glucosidase (GAA), resulting in systemic pathological glycogen accumulation.
The M6PgP-conjugated rGAA had a 16-fold higher content of M6P glycan than rGAA, which resulted in greatly increased cellular uptake and efficient digestion of glycogen accumulated in Pompe disease patient fibroblasts.
This study proposed a rice cell-based glycoengineering strategy using two different mannosidase inhibitors, kifunensine (KIF) and swainsonine (SWA), to increase Man7/8/9 glycoforms of recombinant human acid α-glucosidase (rhGAA), which is a therapeutic enzyme for Pompe disease.