Pompe Disease And The Mutations That Cause It

Briefly, What Is Pompe Disease?

Pompe disease is an inherited neuromuscular disorder in which the muscles of those who are inflicted with it are significantly weakened. Pompe disease symptoms can manifest at any age and they can vary widely on an individual-by-individual basis. The specific cause of muscle weakness is abnormally increased accumulation of the complex sugar glycogen within cells. In many cases, Pompe disease causes premature death soon after birth.

What Is Know About The Genetics Of Pompe Disease And How Do These Genetics Affect Pompe Disease Symptoms?

Pompe disease is attributable to mutations in a gene that is designated GAA, which encodes the protein alpha-glucosidase. The normal function of alpha-glucosidase is to break down the complex sugar glycogen into glucose, which is the main energy source of cells. Mutations in the GAA gene affect the ability of alpha-glucosidase to break down glycogen, and therefore glycogen builds up to abnormally high levels in individuals who are mutant in the GAA gene. Unfortunately, this abnormal build up of glycogen causes damage to the various organs and tissues, and particularly the muscles, of the body.

To date, more than 70 mutations in the GAA have been identified, and it is known that the severity of symptoms that Pompe disease suffer from is dependent of which particular mutation or mutations they inherit. Some mutations drastically, if not completely, limit the function of alpha-glucosidase, typically either by reducing or preventing its synthesis in cells. Since Pompe disease is an autosomal recessive disorder, people who have two copies of the GAA gene which have mutations of this severe kind usually experience early onset Pompe disease. This form of Pompe disease strikes at an early age, and typically within the first few months of life. Infants having the early onset form of Pompe disease generally do not grow as quickly as do normal infants, exhibit feeding problems, have poor muscle function, are prone to respiratory problems and lung infections, and have enlarged tongues and hearts. Sadly, most infants who have early onset Pompe disease die within the first 12 months of life if these symptoms are not properly treated.

Other GAA mutations are not as severe. These mutations somewhat diminish, but do not nearly completely inhibit, the normal function of alpha-glucosidase. People who have who have two copies of the GAA gene which have mutations of this variety generally do not experience Pompe disease symptoms in infancy, but instead first experience these symptoms anywhere from later childhood to about age 50 or so (therefore, this is referred to as the late onset form of Pompe disease). Once Pompe disease first arises in these individuals, muscle weakness, respiratory failure, and death then follow within a few years or so thereafter if the disease is left untreated.

Are There Any Treatment Options For Pompe Disease Sufferers?

Both the early and late onset forms of Pompe disease can be treated with the drug alglucosidase alfa, which has recently received approval for this purpose from the U.S. Food and Drug Administration. Alglucosidase alfa can extend the lives of Pompe disease suffers by reducing excess glycogen storage in cells, which thereby reduces the severity of the symptoms of the disease.

This article is meant only to provide some basic information regarding Pompe disease and is not meant to replace the good advice of your doctor. If you want to learn more about Pompe disease, it is recommended that you contact your doctor.

References

Genetics Home Reference, National Institutes of Health, Pompe Disease: https://ghr.nlm.nih.gov/condition/pompe-disease

Genzyme Corporation, Pompe Community: https://www.pompe.com/en/

National Institute of Neurological Disorders and Stroke, National Institutes of Health, NINDS Pompe Disease Information Page: https://www.ninds.nih.gov/disorders/pompe/pompe.htm