Glycogen storage disease type II (also called Pompe disease or acid maltase deficiency) is a rare genetic disorder caused by a deficiency in the enzyme acid alpha-glucosidase (GAA), which is needed to break down glycogen, a stored form of sugar used for energy. It is the only glycogen storage disease with a defect in lysosomal metabolism, and was the first glycogen storage disease to be identified—in 1932. The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system. Transmission is by autosomal recessive inheritance. Children have a 1 in 4 chance of inheriting the disease when both parents carry the abnormal gene. It is estimated to occur in about 1 in 40,000-300,000 births.

Variants

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Pompe disease has three forms defined by age of onset and progression of symptoms:

Infantile, or early onset, is noticed shortly after birth. Symptoms include severe lack of muscle tone, weakness, and enlarged liver and heart. Mental function is not affected. Development appears normal for the first weeks or months but slowly declines as the disease progresses. Swallowing may become difficult and the tongue may protrude and become enlarged. Most children die from respiratory or cardiac complications before 2 years of age.

Juvenile onset symptoms appear in early to late childhood and include progressive weakness of respiratory muscles in the trunk, diaphragm and lower limbs, as well as exercise intolerance. Intelligence is normal. Most patients do not live beyond the second or third decade of life.

Adult onset symptoms also involve generalized muscle weakness and wasting of respiratory muscles in the trunk, lower limbs, and diaphragm. Many patients report respiratory distress, headache at night or upon waking, diminished deep tendon reflexes, and proximal muscle weakness, such as difficulty in climbing stairs. Intellect is not affected. A small number of adult patients live without major symptoms or limitations

Treatment

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Cardiac and respiratory complications are treated symptomatically. Physical and occupational therapy may be beneficial for some patients. Alterations in diet may provide temporary improvement but will not alter the course of the disease. Genetic counseling can provide families with information regarding risk in future pregnancies.

On April 28, 2006 the US Food and Drug Administration approved a biologics license application (BLA) for Myozyme (alglucosidase alfa, rhGAA), the first treatment for patients with Pompe disease primarily developed by Dr. Y-T Chen of the Institute of Biomedical Sciences in the Academia Sinica (Taipei, Taiwan). Myozyme falls under the FDA Orphan Drug designation and was approved under a priority review. Myozyme is manufactured by Genzyme Corp. in Cambridge, MA, USA. FDA Approval News for Myozyme

The FDA approved Myozyme for administration by intravenous infusion of solution into a vein. The safety and efficacy of Myozyme were assessed in two separate clinical trials in 39 infantile-onset patients with Pompe disease ranging in age from 1 month to 3.5 years at the time of the first infusion.

Prognosis

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The prognosis for individuals with Pompe disease varies according to the onset and severity of symptoms. The disease is particularly lethal in infants and young children.

A new synthetic enzyme called Myozyme is currently being used to replace the missing enzyme. Myozyme helps break down glycogen. The only "cure" for Glycogen Storage Disease Type II will ultimately be gene therapy.

External links

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• Pompe's disease page at Online Mendalian Inheritance in Man
• The website of the Pompe's Group of the Association for Glycogen Storage Disease (UK)
• International Pompe Association - A federation of Pompe disease patient's groups world-wide.
• Genzyme's Pompe Information site
• FDA Approval News for Myozyme

Lysosomal storage diseases | Hepatology | Genetic disorders | Inborn errors of metabolism

Maladie de Pompe