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22 | InTouch SUMMER 2024 Pompe disease is a rare genetic disorder first described in an infant by Dr. Johannes C. Pompe, a Dutch physician, in 1932. Pompe Disease (Acid Maltase Deficiency) YOUR CONDITION IN REVIEW This disorder affects approximately 1 in 40,000 people, though prevalence can vary by population, with some studies suggesting it might be as frequent as 1 in 28,000 in certain groups. Known also as acid maltase deficiency (AMD) or glycogen storage disease type II (GSDII), Pompe disease is an autosomal recessive condition caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). The body uses GAA to break apart and convert glycogen into glucose, which is used to fuel muscles. When the GAA enzyme is deficient, glycogen cannot be broken down within the lysosomes. As a result, glycogen accumulates and causes the lysosomes to enlarge. In some cases, these enlarged lysosomes can burst, releasing glycogen into the surrounding cellular environment. Additionally, the normal cellular recycling processes are disrupted, leading to a buildup of cellular waste. This accumulation of glycogen and cellular waste occurs in all tissues, but most predominately damages skeletal and cardiac muscles. • Glycogen: A chain of sugars stored in the body for energy. • Lysosome: The “mini stomach” of a cell where unwanted substances are broken down. • Enzyme: Proteins that facilitate chemical reactions in the body. Disease Progression Individuals with Pompe disease experience a similar course characterized by progressive damage to tissues over time. The severity of symptoms depends on the amount of active GAA enzyme present. Those with enzyme levels closer to normal typically have a more slowly progressing form known as late- onset Pompe disease, whereas very low or absent levels are associated with the severe, rapidly progressive infantile form. Without treatment, this damage leads to increasing debilitation, organ failure, and potentially death. Infantile-onset Pompe disease manifests within the first few months of life with symptoms such as hypertrophic cardiomyopathy, generalized muscle weakness, and hypotonia, often resulting in death from cardiorespiratory failure by age one. In contrast, late-onset Pompe disease can begin at any age, typically without severe cardiac involvement, and progresses more slowly. Symptoms include progressive skeletal muscle dysfunction, initially affecting muscles of the lower limbs and spine, followed by the diaphragm and accessory breathing muscles. As muscle weakness advances, individuals may require wheelchairs and assisted ventilation. Respiratory failure is a significant cause of morbidity and mortality, with death occurring from early childhood to late adulthood. • Hypertrophic Cardiomyopathy: Thickening of heart muscle, making it more difficult for the heart to pump blood. • Hypotonia: Decreased muscle tone, making infants seem“floppy.” Heart and Lung Management Monitoring heart function is crucial for managing Pompe disease, as it indicates disease progression and response to treatment. Anaesthesia, especially in infants, should be Above: In people with Pompe disease, glycogen cannot be broken down and builds to toxic levels inside cells. Normal Cell Pompe Cell Glucose (source of energy) Glycogen is not broken down Glycogen GAA Enzyme Glycogen GAA Enzyme !