Inborn errors of immunity (IEIs) are a group of rare genetic disorders that impair components of the innate and/or adaptive immune system. While traditionally considered paediatric disorders, it is now increasingly recognised that IEIs can present de novo in adulthood, often with atypical manifestations. Despite this shift, the diagnostic and clinical utility of genetic testing in adults with suspected IEIs remains undercharacterised. This study aims to evaluate the diagnostic yield and clinical implications of immunogenomic testing in adults assessed through the St Vincent’s Hospital immunogenomics clinic over a 23-month period.
We retrospectively audited the medical records of patients engaged with the immunogenomics clinic from 2023 to 2025 inclusive. The primary outcome was the proportion of patients who received a relevant genetic diagnosis. Secondary outcomes included the clinical impact of the genetic testing result.
There were 33 patients (mean 37 years; 17 [52%] female) who underwent genetic testing and received a result. 29 (88%) patients attended the clinic for a clinical cause, 3 (9%) due to family history, and 1 (3%) for confirmation of an unaccredited genetic result. Among tested patients, 7 (21%) received a genetic diagnosis explanatory for their phenotype, and 9 (27%) were found to have a pathogenic variant that was in carrier state of a recessive condition or that did not explain their immune phenotype. 9 (27%) patients had a variant of uncertain significance (VUS) finding, with 3 (9%) being in genes of interest. 8 (24%) returned a negative result. The returned genetic result had an impact on the clinical management of 13 (52%) patients.
The combined immunogenomics clinic demonstrated its effectiveness through the provision of genetic diagnoses, leading to a clinically significant change in management for more than half of tested patients.
