Acid maltase deficiency (AMD) is caused by mutations in a gene called acid alpha-glucosidase, or GAA. Normally, this gene makes a protein called the acid alpha-glucosidase enzyme (also called the acid maltase enzyme). In patients with AMD, these mutations cause the acid alpha-glucosidase enzyme to lose most or all of its function.

The acid alpha-glucosidase enzyme normally functions in muscle cells to break down glycogen, a form of starch that is used to store short-term energy. In people with AMD, the mutated acid alpha-glucosidase enzyme cannot carry out this function. Therefore, glycogen builds up the in the muscles of patients with AMD. This glycogen buildup leads to an expansion of the lysosome (a compartment in the muscle cell that is involved in digesting and degrading materials such as glycogen and other proteins), which may damage and impair the function of the muscle cell. In some cases, glycogen or other substances may begin leaking from the muscle cell.

Because the onset of acid maltase deficiency (AMD) may not occur until later in life, and because many of the physical symptoms (such as fatigue or weakness) are common in other diseases, AMD can be difficult to diagnose. AMD is considered easiest to diagnose in infants, because the symptoms usually develop more rapidly.

GAA testing: One diagnostic test involves measuring the enzymatic function of the protein made by the acid alpha-glucosidase gene (GAA). This enzyme has greatly reduced (or no) activity in patients with AMD. Testing for GAA activity, which is usually performed on a tissue or blood sample, is considered to be the most conclusive way of diagnosing AMD.

Physical signs: In infants, weakness and lack of muscle tone may indicate the presence of AMD.

Heart tests: Because infants with AMD usually have heart defects, heart testing may be performed to assist in diagnosing AMD. Two commonly used heart tests are echocardiography and electrocardiography. In echocardiography, sound waves are bounced off the heart to create a visual image of the heart. This test can be used to check for enlargement or abnormal thickness of the heart, which would indicate AMD. In electrocardiography, electrodes are placed on the chest to monitor heart rhythm and heartbeat frequency. Patients with AMD often have an irregular heart rate.

Serum CK test: Tests that measure an enzyme called creatine kinase (CK) in the blood can be used to identify muscle defects. CK is an enzyme that helps carry out a chemical reaction on creatine, a substance used by the body for energy. CK levels rise in the blood in patients with AMD when muscle cells break open, but CK levels may also rise due to other factors, such as a heart attack or normal exercise. Therefore, the serum CK test may not be able to diagnose a patient specifically with AMD, because other diseases that affect the muscles, as well as normal exercise, also result in increased levels of serum CK.

Genetic testing: Mutations in the acid alpha-glucosidase gene are known to cause AMD. Genetic tests can be used to check for these mutations and diagnose AMD. These tests may be used to confirm a diagnosis if there is a family history of AMD, or if symptoms of AMD are present.

The time of onset of acid maltase deficiency (AMD) varies among patients, and can occur in infants, children, or adults. The infant onset form is considered to be the most severe. In general, the later the onset of AMD, the more slowly it will progress, and the less severe the symptoms. This is because patients with later onset AMD may have less severe mutations in the acid alpha-glucosidase gene.

Patients with AMD have a buildup of glycogen in their muscles. This leads to a weakening of muscles that progressively worsens over time. In patients with AMD, the glycogen buildup primarily occurs in a compartment of the muscle cell called the lysosome, which is involved in digesting and degrading other materials (such as proteins) in the cell. This glycogen buildup leads to an expansion of the lysosome, which may damage and impair the function of the muscle cell. Muscles of the hips, upper legs, shoulders, upper arms, trunk, and diaphragm may all grow progressively weaker in patients with AMD.

The glycogen buildup may impair cardiac and respiratory muscles, which may lead to serious complications. Cardiac muscles are most likely to be affected in infants, and not as likely to be affected in individuals who develop the disease later in life. Hearts of infants with AMD become severely thickened and enlarged, making it more difficult to pump blood.

Infants who develop AMD may display feeding problems, poor weight gain, a lack of muscle tone, and enlarged hearts and tongues.

Patients who develop AMD as children or adults may experience fatigue, as a result of muscle weakness, and high blood pressure.

Cardiac/respiratory problems: Large amounts of glycogen may build up in the respiratory and cardiac muscles of patients with acid maltase deficiency (AMD). This can lead to respiratory and cardiac failure, and ultimately death.

In AMD onset in infants, heart and respiratory complications usually cause death by the age of one year. Hearts of infants with AMD become severely thickened and enlarged, making it more difficult to pump blood.

In AMD onset in children or adults, respiratory failure is a more common complication than cardiac failure. The respiratory muscles may become weakened, which can lead to difficulty breathing. Children and adults diagnosed with AMD usually have a life expectancy from 10 to 20 years after symptoms begin to appear.

Lung infections, such as bronchitis or pneumonia, may develop more easily in patients with AMD.

Muscle weakness can make it difficult for patients to perform everyday tasks, such as eating or walking.

Acid maltase deficiency (AMD) is a recessive inherited genetic condition. Normal individuals have two copies of most genes (one inherited from the father and one from the mother). In a recessive genetic disorder, both copies of a certain gene need to be defective for the condition to manifest itself. It has been shown that mutations in the acid alpha-glucosidase gene may cause AMD. People who only have one mutated gene are called "carriers." If only one parent is a carrier, none of the children will have AMD, but 50% of the children will also be carriers; if both parents are carriers, then there is a 50% chance that a child will be a carrier and a 25% chance that a child will have AMD.