Olivier Gilliaux, BelgiumCHU de Charleroi Pediatrics
Presenter Of 1 Presentation
SEVERE INFLUENZA A VIRUS INFECTION IN A PATIENT WITH A PATHOGENIC TLR3 MUTATION
Background and Aims
Toll-like receptor 3 (TLR3) binds double stranded RNA which via TRAF3 and TBK1 leads to IRF3 phosphorylation and induction of a type I IFN response. Defects in TLR3 have been described as genetic etiology of Herpes Simplex Virus encephalitis (HSE) , with variable penetrance.
We describe here a patient with TLR3 mutation (p.Pro554Ser) who presented with several severe viral infections including severe Influenza A virus (IAV), but no HSV encephalitis.
Patient is a girl from Belgian non-consanguineous parents. She presented at 5 weeks of age a severe Influenza A infection that required non-invasive ventilation and admission to pediatric intensive care (PICU). 2 months later, she developed a severe bronchiolitis due to Respiratory Syncytial Virus (RSV) and required again non-invasive ventilation at PICU. She was furthermore hospitalized between 1 and 2 times a month for respiratory or gastro-intestinal disease (including Rotavirus infection despite immunization). At the age of 6 months old, hypogammaglobulinemia was found and immunoglobulins substitution was started. Infection frequency slowly decreased. She is now 3.5 years old, alive and well. A NGS panel for immune deficiencies was started and surprisingly, returned a heterozygous TLR3 mutation (p.Pro554Ser), reported pathogenic in the context of HSE. WES did not reveal alternative etiologies for the observed phenotype.
We here report a pathogenic TLR3 (p.Pro554Ser) mutation in a patient with severe flu and other viral infections, but not HSE. This broadens the phenotype observed in patients with this TLR3 mutation.