Pompe disease, a rare but important genetic condition

As I plan to become a clinical geneticist, I should write more often about genetic conditions. But I don’t want to duplicate the articles of Wikipedia, my aim is to provide useful sources of information. Pompe disease is a rare disorder caused by the deficiency of the acid alpha-glucosidase enzyme. It’s inherited in an autosomal recessive manner. The patients can’t break down glycogen. According to the Wiki article:

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.

I’d like to show you the main characteristics of the disease and of the diagnosis.

Head lag caused by muscle weakness

Cardiomegaly in Infant


The heart of a 9 month old child who died of congestive failure. (Original material by Horton Johnson)

Why do we have to talk about Pompe? The reason is diagnostic delay. The diagnosis often poses a dilemma due to the rarity of the disease, the variable rates of progression and the unspecific phenotypic features. What kind of disorders do we have to list as a part of the differential diagnosis?

  • Spinal muscular atrophy
  • Hypothyroidism
  • Endocardial fibroelastosis
  • Myocarditis
  • Congenital muscular dystrophy
  • Glycogen storage diseases
  • Mitochondrial, peroxisomal diseases
  • Danon disease
  • Myasthenia gravis, Becker’s muscular dystrophy

Just take a look at the diagnostic delay diagram, there are from 2 to 4 years between the first symptoms and the diagnosis:


How can we confirm diagnosis? An acid-glucosidase (GAA) assay can be performed on skin fibroblasts or muscle biopsy. A non-invasive and relatively reliable test is GAA assay in blood collected on filter paper. But laboratory testing and molecular analysis must be also taken into consideration.

Some words about the treatment. Of course, genetic counseling can help parents as it provides them information about a possible future pregnancy. According to the wiki article:

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 while he was at Duke University. Myozyme falls under the FDA Orphan Drug designation and was approved under a priority review.

Although Pompe disease is a rare condition (estimated to occur in about 1 in 40,000-300,000 births), it should get much more attention as the diagnostic delay still means a crucial problem in treating these children.