Genetic testing is typically reserved for patients with unexplained clinical feature(s) and/or a family history that may allude to a genetic explanation, or for individuals that are deemed ‘high-risk’ because of an identified pathogenic variant in their family.¹ In the context of Pompe disease, either scenario can necessitate a genetic test, although clinicians may first seek to establish a deficiency in GAA enzyme activity through an enzyme assay.²

If a physical examination presents with unexplained symptoms, the first step is to obtain a detailed medical family history. This should include drawing a three-generation family tree (genetic pedigree).³

The next step is to consult the genetic test directory for the nation in which you are working. Test directories for Ireland, Wales, Scotland and Northern Ireland can be accessed using these links.

Genomic testing in Ireland

Genomic testing in the devolved nations

The GAA gene for Pompe disease is included in nine panels.⁵ Click on the heading to reveal the full list.

Although many of these panels are designed for infant-onset Pompe disease, some may be used for late-onset Pompe disease, depending on the presentation.

For example, let’s say a patient presents with progressive myopathy and a history of fatigue and shortness of breath. This leads to a suspicion of a muscular dystrophy or an overlapping condition, so the clinician decides that genomic testing is warranted. The clinician goes on to refer the patient for the R82 panel which includes GAA.^4,6

Consent and counselling

When undertaking genetic testing, it is the responsibility of the referring specialist to record any discussions with the patient and obtain informed consent. This can be documented in the patient notes, but best practice is to complete a Record of Discussion (RoD) form.⁷

Pre-genetic test counselling may also be necessary, as it ensures patients are informed about the test itself, and what the results might mean.⁸

Arranging a genetic test

Genetic test requests are submitted using a Genetic Testing Request Form. The form will specify any sampling requirements and provide prompts for all necessary information.⁹ Forms will vary by trust and are available on local Genomic Laboratory Hub websites.

The turnaround time for the results varies, ranging from a few weeks for a single gene test to several months, depending on test complexity and lab workload. The laboratory will be able to advise on the likely turnaround time.⁹

Interpreting the results

There are four possible findings for any diagnostic genetic test, which are summarised below.¹⁰ Click on the headings to find out more.

The results of a genetic tests are typically returned to the requesting clinician by post or email. They are then shared with the patient at the start of their next appointment, once they have confirmed they are ready to hear them.

Results should be stated in clear, simple terms. It is important to remember that a genetic test result (such as a Pompe disease diagnosis) can provoke a range of emotions and can have a large impact, both positive and negative, on family members.

If a Pompe disease diagnosis is established, family members may wish to undergo carrier testing, as Pompe is inherited in an autosomal recessive manner.