Acid Maltase Deficiency

Definition

Definition of Acid Maltase Deficiency
Acid maltase deficiency (AMD), also known as Pompe disease, is a genetically inherited disease that affects muscle function. Inherited diseases are passed on from parents to a child. Patients with AMD have a defect, or mutation, in a gene that functions in muscles, called the acid alpha-glucosidase (GAA) gene. This genetic mutation causes a substance called glycogen to build up in the muscles of patients with AMD. Glycogen is a form of starch that is used to store short-term energy.

Symptoms

Symptoms of Acid Maltase Deficiency
Slowly progressive weakness of respiratory muscles and muscles of the hips, upper legs, shoulders and upper arms; cardiac involvement common in infantile-onset form.

Causes

Causes of Acid Maltase Deficiency
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.

Diagnosis

Diagnosis of Acid Maltase Deficiency
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.

1. 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.
2. Physical Signs: In infants, weakness and lack of muscle tone may indicate the presence of AMD.
3. 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.
4. 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.
5. 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.

Prognosis

Prognosis of Acid Maltase Deficiency
The prognosis for patients with Pompe disease varies symptomatically, however, without treatment, the disease can be lethal during infancy and early childhood. Treatment with Myozyme in enzyme replacement therapy has had positive outcomes in prolonging ventilator-free survival rates and has the potential to decrease mortality and disability rates associated with infantile AMD.

Treatment

Treatment of Acid Maltase Deficiency
Complications associated with AMD are treated symptomatically and physical therapy programs are available for patients and may be beneficial. The first treatment for patients with Pompe disease, known as Myozyme, was developed and approved by the US Food and Drug Administration in 2006. Myozyme is a recombinant variety of the human enzyme acid alpha-glucosidase and helps with the break down of glycogen.