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 genetic 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, testing for IOPD can take the form of testing multiple systems to investigate symptoms further or undergoing tests that actually confirm 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 genetics to determine if there is a change (pathogenic variant) in the gene for the GAA enzyme.

Testing the GAA gene for pathogenic variants and a multigene testing panel, which can test for pathogenic variants related to many different neuromuscular disorders, could be something your baby’s doctor recommends at any point along the diagnostic journey based on his or her clinical judgement.

GAA enzyme level testing:

  • Patients with classic 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 blood test for GAA enzyme activity can use 3 different methods using a blood sample:
  • Mixed white blood cells (leukocytes) from whole blood
  • Purified white blood cells (lymphocytes) from whole blood
  • Dried blood spot (DBS) sample which is blood dried on filter paper for analysis
  • The DBS test is commonly used due to its accuracy and convenience

Genetic testing:

  • A test that can provide more information about the genetic defect in the GAA gene that causes less enzyme to be produced is called mutation analysis, or genotyping, and is confirmation of IOPD
  • Testing can be done on blood or saliva
  • Changes in the GAA gene may give information on how severe the disease will be (ie, how much enzyme deficiency there is and how severe the symptoms are likely to be)
  • If clinical judgment dictates, your baby’s doctor may also order a multigene test panel to investigate the possibility of Pompe disease and other inherited disorders simultaneously