Guideline for the Diagnosis and Management of Heritable IFNAR1 Deficiency in Oceania

Autosomal recessive interferon alpha and beta receptor subunit 1 (IFNAR1) deficiency is a rare and heritable inborn error of immunity (IEI) predisposing individuals to severe and life-threatening viral infections. It is more common in people of Western Polynesian ancestry, with estimates of around one in six thousand live births affected, due to being homozygous for or having two copies of the regionally relevant pathogenic IFNAR1 variant c.1156G>T, p.Glu386*. IFNAR1 deficiency confers an increased risk of severe and life-threatening infections caused by naturally circulating viruses including influenza, SARS-CoV-2, herpes simplex virus, respiratory syncytial virus (RSV), arboviruses and viruses in live attenuated vaccines (LAVs) including measles-mumps-rubella (MMR) and yellow fever. Complications including virus induced systemic hyperinflammation (VISH) are associated with significant mortality. This document outlines expert consensus regarding early identification, diagnostic workup and management of IFNAR1 deficiency in Australia, Aotearoa New Zealand and Western Pacific nations.