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.^1,2 In the context of Fabry disease, either scenario can necessitate a genetic test. 

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 GLA gene for Fabry diseased is included in 11 panels, including the single R335 Fabry disease test and other presentation-specific panels.⁵ Click on the heading to reveal the full list.

For example, let’s say a patient presents with unexplained obstructive hypertrophic cardiomyopathy on cardiac MRI. Searching for ‘hypertrophic cardiomyopathy’ in the test directory recommends the gene panel R131, which includes GLA.⁴

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.

Confirmed genetic diagnosis

A pathogenic or likely pathogenic variant(s) consistent with the patient’s condition is identified.¹⁰ In the case of Fabry disease, a pathogenic GLA variant is identified.

Incidental findings

A variant is discovered but is unrelated to the reason for requesting the genetic test.¹⁰

No significant findings

No significant variant(s) associated with the patient’s condition is identified. However, this result is reliant on current knowledge and understanding, so it does not necessarily mean that the individual does not have an underlying genetic cause for their condition. In these instances, clinical management depends on the patient’s clinical and/or family history.¹⁰

Variant(s) of uncertain significance

A variant is identified, however there is insufficient information to confirm whether the variant identified is natural genomic variation or is relevant to the patient’s condition. No conclusions can be made.¹⁰ Variants can be reclassified over time as more data become available.

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 Fabry disease diagnosis) can provoke a range of emotions and can have a large impact, both positive and negative, on family members.

If a Fabry disease diagnosis is established, it is crucial that family cascade screening is initiated to identify any affected family members.