Pompe Disease Testing

What is Pompe Disease?

Pompe disease is a rare autosomal recessive disorder caused by mutations in the GAA gene.1 Also known as acid maltase deficiency, Pompe disease is a chronic and progressive lysosomal storage disorder resulting from a partial or total deficiency of the lysosomal enzyme acid α-glucosidase, a key component for glycogen degradation.1,2  The progressive glycogen accumulation results in severe damage to muscle structure and function.2  While this rare disease predominantly affects cardiac and skeletal muscle, it has wide variability with the emergence of non-muscle phenotypes including the smooth muscle of the gastrointestinal tract and blood vessels.2,3

Pompe disease consists of a broad spectrum of phenotypes depending on the age of onset and may present in infancy or young and adult ages.1,2 

Pompe disease is divided into two forms, infantile-onset which are referred to as infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD)3

  • Considered the classic form of Pompe disease, IOPD begins at birth or within the first few months of life.1  Characterized by elevated CK levels,4 severe muscle weakness, respiratory insufficiency, and cardiomyopathy, IOPD can lead to death within the first year of life if left unmanaged.1,2  Symptoms that may be indicative of this rare disease can include delayed or regressed motor development, hypertrophic cardiomyopathy, alteration of intestinal tract with macroglossia (which may cause swallowing defects), and hypotonia (“floppiness”). When affected by the severe form of Pompe disease, infants may require mechanical support to breathe.1
  • Occurring during childhood or adulthood, the second form of Pompe disease, LOPD, has a more insidious course and presents primarily as a muscle disease.CK levels may or may not be elevated4 and LOPD can manifest with myopathy affecting gait and respiratory decline.2 Muscle biopsy results in LOPD cases may show vacuolated fibres filled with glycogen as seen on PAS or acid phosphatase staining.3 However, due to high variability within muscle fibres, false negative results may occur and thus normal muscle biopsy results may not exclude a Pompe disease diagnosis.1 Signs and symptoms that may indicate LOPD differ widely but include progressive proximal muscle weakness, skeletal myopathy, exercise intolerance, respiratory infections, dyspnea and breathing failure, and swallowing difficulties.1,2  


What is the Incidence of Pompe Disease?

The traditional estimate of overall incidence is approximately 1/40,000, however, incidence can vary widely within different ethnic groups. Newborn screening in the United States has shown an incidence of Pompe disease of 1/23,596, 1/16,095 and 1/10,152 in Illinois, Pennsylvania and Missouri respectively.3

The Roadmap2Rare Diagnostic Program Eligibility

This rare disease testing program is designed for HCPs with eligible patients when there is clinical suspicion of Pompe disease. The program includes single disorder testing for Pompe (acid α-glucosidase enzyme assay with reflex to GAA sequencing if deficient) and two multi-gene NGS panels that include GAA (a 122-gene Muscle Disorders panel and 60-gene Hypertrophic Cardiomyopathy Panel).

*Note: this diagnostic program is not appropriate for carrier testing.

What is the Pompe Disease Test?

For single disorder testing, the algorithm is as follows:

  1. Acid α-glucosidase is assayed
  2. If enzyme levels are found to be deficient, GAA sequencing is performed (along with copy number variant analysis if required)

In the event that either GAA sequencing or enzyme assay activity testing has been performed previously, individual tests can be ordered.

For infants with Pompe positive presumptive newborn screens or symptoms of infantile-onset Pompe disease, expedited GAA sequencing is available.


  1. Taverna S, et al. Aging (Albany NY). 2020;12(15):15856–15874.
  2. Davison JE. J Mother Child. 2020;24(2):3–8.
  3. Stevens D, et al. Curr Treat Options Neurol. 2022;24(11):573–588.
  4. Kishnani PS, et al. Genet Med. 2006;8(5):267–288.

The Roadmap2Rare Diagnostic Program is not intended to and should not interfere in any way with a clinician’s or patient’s independent judgment and freedom of choice in the testing and treatment options for these diseases. Clinicians and patients should always consider the full range of testing and treatment options and select those most appropriate for the individual patient. The identifying information of patients and clinicians is not shared with Sanofi Canada.