About Pompe Disease

What is Pompe disease?

  • Pompe disease is a rare neuromuscular disorder.
  • Approximately 60-70 people in Canada are diagnosed with Pompe disease. There are likely many more that have not been diagnosed.
  • There are two types of Pompe disease — infantile-onset and late-onset Pompe disease.
  • Pompe is an inherited disease, so it isn’t uncommon for siblings or other relatives to be affected. If one person in your family is affected, it may be appropriate to test other family members.
  • Treatment is available for Pompe disease that has changed this once deadly condition to one that is manageable with the right health care team in place.

What Causes Pompe disease?

This genetic disease causes an inadequate level of the enzyme acid alpha-glucosidase (GAA).

(GAA) breaks down glycogen to glucose. [Hers 1963] Without the GAA enzyme, glycogen can accumulate in the body and cause damage – particularly to muscle tissue. The severity and onset of the symptoms will depend on the level of GAA enzyme present. In the most severe cases, infantile-onset Pompe disease, there is no enzyme present (or extremely low levels). These infants have severe muscle weakness and will likely not live to see their first birthday without treatment. In children and adults with late-onset Pompe disease, they have some enzyme present and the symptoms can appear in early childhood or much later in adulthood. These individuals can have a wide range in symptom severity.

Unfortunately, Pompe disease is a progressive disease. That means that any symptoms that are present will worsen without proper treatment.

How common is it?

It is estimated that 5,000 – 10,000 people live with this disease in the world. There are approximately 60-70 people in Canada currently diagnosed with Pompe disease. These estimates are likely very conservative. Recent newborn screening data indicates that Pompe disease may be more than twice as common as once thought.

The genetics of Pompe disease

Pompe disease is an inherited disease. More specifically, it is an autosomal recessive genetic disease. For a person to develop the condition, they had to receive a bad copy (variant) of the gene from each of their parents. Since it is a recessive genetic condition, if you have 1 gene variant for Pompe disease, you will not have any symptoms (or very few). People that have that 1 gene variant are carriers of the condition and are often not aware they are carriers. If a carrier has a child with another carrier, there is a 25% chance their offspring will have Pompe disease. There is a 50% chance their offspring will be a carrier and a 25% chance they will neither have the condition nor be a carrier.

Autosomal recessive

The gene involved in Pompe disease is the GAA gene, present on chromosome 17.[Lim 2014; Berger 2017] Several variants of the GAA gene have been identified. The type of variant can indicate the severity of the condition – that is, the variant will impact how much of the enzyme GAA can still be produced. For example, variants that involve a deletion of exon 18 of the GAA gene can result in negligible GAA enzyme activity, This would be associated with the more-severe infantile-onset Pompe disease. [Leslie 2017] In contrast, variants that allow some GAA enzyme to be produced would be associated with late-onset Pompe disease. [Leslie 2017]  The correlation/causation between the variants and the severity of the disease is not well known at this time – that is due to a combination of factors. First, there are over 900 known variants in the GAA gene. Second, each parent can contribute their own GAA variant, so offspring with 2 different GAA variants can impact GAA enzyme levels differently. And third, the Pompe disease population is a very small and diverse group of people so we’re learning over time how gene variants can impact a particular person and their symptoms.

Other names for Pompe disease

Acid alpha-glucosidase deficiency

Acid maltase deficiency (AMD)

GAA deficiency

Glycogenosis II

Glycogen storage disease type II (GSD II)

Lysosomal alpha-glucosidase deficiency