"Extraordinary Measures" Brings Attention to Pompe Disease
The film Extraordinary Measures hits movie theaters this weekend, telling the story of a father’s efforts to save his two children. Both children were born with the fatal genetic disorder Pompe Disease.
Pompe disease is a rare, inherited disorder that disables the heart and muscles. This often fatal disorder is estimated to affect 1 in every 40,000 births. Pompe disease is inherited in an autosomal recessive manner. This means that an affected individual must inherit an abnormal allele from both parents.
Pompe disease is named for Dutch pathologist Joannes C. Pompe. She first defined the disease in 1932 in a seven-month-old infant who died of idiopathic cardiac hypertrophy and was found to have massive glycogen accumulation, especially in the skeletal and cardiac muscles.
It wasn’t until 1963 that the disease was linked to an inherited deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Normally, the body uses GAA to break down glycogen, a stored form of sugar used for energy. In Pompe disease, the mutations in the GAA gene reduce or completely eliminate this essential enzyme. Excessive amounts of glycogen accumulate everywhere in the body, but the heart and skeletal muscles are the most seriously affected.
Researchers have identified 70 different mutations in the GAA gene that cause the symptoms of Pompe disease. The age of onset and severity of the disorder varies greatly and are are related to the degree of enzyme deficiency.
Pompe disease is classified as either early onset (infantile) or late onset (juvenile/adult). Early onset Pompe disease is the result of complete or near complete deficiency of GAA. Symptoms begin in the first months of the infant’s life, with feeding problems, poor weight gain, muscle weakness, floppiness, and head lag. Most babies with Pompe disease die from cardiac or respiratory complications before their first birthday.
Late onset Pompe disease results when there is only a partial deficiency of GAA. Onset of symptoms can be as early as the first decade of childhood or as late as the sixth decade of adulthood. The primary symptom is muscle weakness progressing to respiratory weakness. Death from respiratory failure is common.
A diagnosis of Pompe disease can be confirmed by screening for the common genetic mutations or measuring the level of GAA enzyme activity in a blood sample -- a test that has 100 percent accuracy. Once Pompe disease is diagnosed, testing of all family members and consultation with a professional geneticist is recommended. Carriers are most reliably identified via genetic mutation analysis.
Treatment of Pompe disease includes a combination of disease-specific and supportive therapies. Pompe patients are best followed by a multidisciplinary team headed by a physician with experience treating the disease or similar disorders.
Currently, the only treatment for this devastating disease is enzyme replacement therapy using a drug called alglucosidase alfa (Myozyme©) received FDA approval for the treatment of Pompe disease on April 28, 2006. It has been shown to decrease heart size, maintain normal heart function, improve muscle function, tone, and strength, and reduce glycogen accumulation.