Pompe disease is a rare genetic disorder of glycogen metabolism that is caused by the absence or marked deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). This disease is also known as glycogen storage disease type II, GSD II, glycogenosis type II, or acid maltase deficiency. GAA is necessary for proper muscle functioning and is used by the heart and muscle cells to convert a form of sugar called glycogen into energy. Without the GAA enzyme action, glycogen builds up in the cells of the heart, skeletal muscles, and hepatic tissues. Ultimately, these body organs are weakened by the intralysosomal accumulation of glycogen. Pompe disease encompasses a range of phenotypes, each including myopathy, but with significant variability in the age of onset, organ involvement, and clinical severity.
Infantile-onset Pompe disease occurs in an estimated 1 in every 40,000 to 300,000 births. Symptoms begin in the first months of life, with feeding problems, poor weight gain, muscle weakness, floppiness, and head lag. The primary symptom is heart and skeletal muscle weakness, which leads to the development of cardiomyopathy, progressing respiratory weakness, and death, usually from respiratory failure. Younger individuals generally have a much more aggressive form of the disease.
Juvenile/adult-onset Pompe disease results in intralysosomal accumulation of glycogen that is limited primarily to skeletal muscle, resulting in progressive muscle weakness. The onset can be as early as the first decade of childhood or as late as the sixth decade of adulthood. The primary symptom is muscle weakness progressing to respiratory weakness and death from respiratory failure over several years. The heart is usually spared.
Enzyme replacement therapy has been shown to decrease heart size, maintain normal heart function, improve muscle function, tone, and strength, and reduce glycogen accumulation. Enzyme replacement therapy is currently not recommended for individuals with no symptoms or objective signs (proximal muscle weakness or reduced FVC in wither upright or supine position) of Pompe disease.
Alglucosidase alfa (Lumizyme®) is FDA-approved for individuals with Pompe disease (GAA deficiency). The safety and efficacy was assessed in 57 treatment-naïve individuals with infantile-onset Pompe disease, aged 0.2 months to 3.5 years at first infusion, in three separate clinical trials. In all three trials ventilator-free survival improved significantly compared with an untreated historical control. The safety and efficacy of alglucosidase alfa (Lumizyme®) was also assessed in 90 individuals with juvenile/adult-onset Pompe disease in a randomized, double-blinded, placebo-controlled trial. Alglucosidase alfa (Lumizyme®) was shown to have a significant increase in forced vital capacity (FVC) and the distance an individual with juvenile/adult-onset Pompe disease can walk within 6 minutes (6 minute walk test).
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