Testing Options Infantile-onset Pompe Disease

Many routes can lead to an infantile-onset Pompe disease (IOPD) diagnosis.

A family history of Pompe disease may have prompted genetic counseling and in-utero testing of a baby or newborn screening could have been performed shortly after birth. If signs and symptoms suggest Pompe disease, additional tests to confirm a diagnosis may be performed.

Testing to Confirm IOPD

As described in more detail in the Diagnostic Journey of IOPD, a diagnosis of IOPD is typically made when a very low amount of acid alpha-glucosidase, or GAA, enzyme is detected in the blood or tissue. The recommended confirmatory test for IOPD uses genetic analysis to determine if there are changes (pathogenic variants) in the gene for the GAA enzyme. 

GAA enzyme level testing:

  • Patients with IOPD typically have GAA enzyme <1% of normal
  • Testing levels of GAA enzyme can be performed on 3 types of body tissue: skin, muscle, and blood
  • Skin and muscle tests are not used as often as blood tests because they are inconvenient, time-consuming, more expensive, and require an invasive biopsy
  • The dried blood spot (DBS) test is commonly used due to its accuracy and convenience

Genetic testing:

  • Genetic testing of the GAA gene can identify the specific genetic alterations and is often done after blood testing has revealed deficient GAA enzyme

  • The combination of genetic variants in the GAA gene may provide information on disease severity