Acid maltase, also known as acid alpha-glucosidase (GAA), is an enzyme located within lysosomes, which are small cellular compartments responsible for recycling various substances. This enzyme is encoded by the GAA gene in humans, found on chromosome 17.
Function of Acid Maltase
Acid maltase plays a role in the breakdown of glycogen, a stored form of energy in the body. It acts within lysosomes to convert glycogen into glucose, a simpler sugar for energy. This process involves breaking down the alpha-1,4 and alpha-1,6 linkages found in glycogen, as well as in other related sugars like maltose and isomaltose. This conversion makes stored energy accessible for cellular functions.
Understanding Acid Maltase Deficiency
When acid maltase is deficient, the body cannot properly break down glycogen within the lysosomes. This leads to glycogen accumulation inside lysosomes, resulting in cellular damage and tissue destruction. This accumulation is particularly pronounced in muscle tissues, including skeletal, cardiac, and respiratory muscles. The condition directly caused by this enzyme deficiency is known as Pompe disease, also referred to as Glycogen Storage Disease Type II (GSD II). Pompe disease is a genetic disorder inherited in an autosomal recessive manner, meaning an individual must inherit a mutated GAA gene from both parents to develop the condition.
Symptoms of Deficiency
Symptoms of acid maltase deficiency vary by age of onset, categorized into infantile-onset and late-onset forms. Infantile-onset Pompe disease often appears shortly after birth. It is characterized by severe muscle weakness, poor muscle tone, and an enlarged heart. Affected infants may also experience feeding difficulties, failure to thrive, and respiratory problems, leading to early mortality if untreated.
Late-onset Pompe disease can manifest in childhood, adolescence, or adulthood, and generally progresses more slowly than the infantile form. Common symptoms include progressive muscle weakness, particularly in the hips, upper legs, shoulders, and upper arms, which can lead to difficulties with mobility and gait. Respiratory issues, such as shortness of breath and recurrent infections, are also common due to weakened breathing muscles. While cardiac involvement is less frequent in the late-onset form compared to the infantile form, some individuals may experience irregular heartbeats.
Diagnosis and Treatment
Diagnosing acid maltase deficiency involves biochemical assays for enzyme activity, a definitive diagnostic tool. These tests measure acid alpha-glucosidase activity in various samples, including dried blood spots, leukocytes, cultured skin fibroblasts, or muscle tissue. Genetic testing, which identifies mutations in the GAA gene, is the standard for confirming a diagnosis and provides information about the specific type of Pompe disease. Muscle biopsies may also be performed to observe glycogen accumulation within lysosomes.
Treatment for acid maltase deficiency focuses on enzyme replacement therapy (ERT), which involves intravenously administering a manufactured version of the acid alpha-glucosidase enzyme. Medications like alglucosidase alfa and avalglucosidase alfa are examples of these enzymes, which help reduce glycogen buildup and improve muscle function. ERT has improved outcomes for individuals with Pompe disease, particularly in infantile-onset cases, reversing cardiomyopathy and increasing survival. Supportive care, including physical therapy and respiratory support, also helps manage the condition by addressing specific symptoms and improving quality of life.