Glucosidase acid-1,4-alpha deficiency

Glucosidase acid-1,4-alpha deficiency, also known as Pompe disease or Glycogen storage disease type II (GSD II), is a rare, inherited lysosomal storage disorder that affects the muscles and heart. It results from the buildup of glycogen in the body's cells, caused by the deficiency of the enzyme acid alpha-glucosidase (GAA). This enzyme is necessary for breaking down glycogen into glucose, which cells use for energy. Without enough functional GAA, glycogen accumulates in tissues, especially in muscles, impairing their ability to function properly.

Causes

Glucosidase acid-1,4-alpha deficiency is caused by mutations in the GAA gene, which provides instructions for making the enzyme needed to break down glycogen. The condition is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disease.

Symptoms

The symptoms of Pompe disease can vary widely among affected individuals and can appear at any age. The disease is typically classified into two main forms based on the age of onset: the infantile-onset form and the late-onset form.

• Infantile-onset form: This form is more severe and is characterized by muscle weakness, poor muscle tone, an enlarged liver, failure to thrive, and heart defects. If left untreated, it can lead to heart failure and death within the first year of life.
• Late-onset form: Symptoms may appear later in childhood, adolescence, or adulthood. This form is generally less severe but still significantly impacts quality of life. Symptoms include progressive muscle weakness, particularly in the trunk and legs, respiratory difficulties, and reduced endurance.

Diagnosis

Diagnosis of Pompe disease involves a combination of clinical evaluation, family history, and laboratory tests. Key diagnostic tests include:

• Enzyme activity assays to measure the activity of acid alpha-glucosidase in the blood or other tissues.
• Genetic testing to identify mutations in the GAA gene.
• Muscle biopsy to look for glycogen accumulation in muscle cells.

Treatment

While there is no cure for Pompe disease, treatments are available that can help manage symptoms and improve quality of life. The primary treatment is enzyme replacement therapy (ERT) with alglucosidase alfa (Myozyme®), a recombinant form of human GAA. ERT has been shown to improve muscle function and heart structure in many patients, especially if started early. Other treatments focus on managing specific symptoms and may include physical therapy, respiratory support, and nutritional support.

Prognosis

The prognosis for individuals with Pompe disease varies depending on the form of the disease and when treatment is initiated. Early diagnosis and treatment initiation are critical for improving outcomes, especially in the infantile-onset form. With appropriate treatment, individuals with the late-onset form can manage symptoms effectively and maintain a higher quality of life.

Glucosidase acid-1,4-alpha deficiency Resources
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