Glycogen storage disease type II

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&mdash;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; therefore, 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
Pompe disease has historically been divided into three forms defined by age of onset and progression of symptoms (see below). More recently there has been a trend to divide the disease into two groups: infantile onset (involving the massive enlargement of the heart) and late onset (no heart enlargement):

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.

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
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. Yuan-Tsong Chen (陳垣崇) while he was at Duke University (Dr. Chen is currently the director of the Institute of Biomedical Sciences, 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.

Myozyme costs an average of $300,000 a year, and must be taken for the patients' entire life. Some insurers have refused to pay for it.

On August 14, 2006, Health Canada approved Myozyme for the treatment of Pompe disease. On June 14, 2007 the Canadian Common Drug Review issued their recommendations regarding public funding for Myozyme therapy. Their recommendation was to provide funding to treat a very small subset of Pompe patients (Infants less one year of age with Cardiomyopathy). The vast majority of developed countries are providing access to therapy for all diagnosed Pompe patients.

Prognosis
The prognosis for individuals with Pompe disease varies according to the onset and severity of symptoms. Without treatment the disease is particularly lethal in infants and young children.

Myozyme (alglucosidase alfa), a recombinant form of the human enzyme acid alpha-glucosidase, is currently being used to replace the missing enzyme. Myozyme helps break down glycogen. In a study which included the largest cohort of patients with Pompe disease treated with enzyme replacement therapy (ERT) to date findings showed that Myozyme treatment clearly prolongs ventilator-free survival and overall survival in patients with infantile-onset Pompe disease as compared to an untreated historical control population. Furthermore, the study demonstrated that initiation of ERT prior to 6 months of age, which could be facilitated by newborn screening, shows great promise to reduce the mortality and disability associated with this devastating disorder.

The only "cure" for Glycogen Storage Disease Type II may ultimately lay in future technologies such as gene therapy.