Efimia Papadopoulou-Alataki, Greece
Aristotle University of Thessaloniki PediatricsPresenter of 1 Presentation
IDENTIFICATION OF A HETEROZYGOUS VARIANT IN THE IRAK-4 GENE IN A 17-YEAR OLD FEMALE PATIENT
Abstract
Background and Aims
IRAK-4 is an active kinase associated with the IL1 receptor. It is involved in the signaling pathway of the cellular activation in response to Toll like receptor (TLR) agonists and the IL-1/IL-18 superfamily. Irak-4 deficiency is an autosomal recessive defect of innate immunity. We report a 17-year old female patient with recurrent infections and numerous hospitalizations since the age of 3 years. At the age of 7 years she was investigated for recurrent bacterial infections affecting the skin (Staphylococcus aureus) and the respiratory tract such as sinusitis, otitis media and mastoiditis (S. pneumoniae). She was also diagnosed with intellectual disability within autism spectrum, obesity and hypothyroidism. Her immunological investigation was normal except low immunoglobulin levels (IgG=717mg/dl, IgA=26,60mg/dl, IgM=50,80mg/dl). A prophylactic administration of immunoglobulins was started and lasted 5 years resulting in significant reduction of infections. Since the age of 12 years she is no longer suffering from infections and her immunoglobulin levels are normal.
Methods
Whole exome sequencing was performed on the patient. DNA-analysis was done using Otogenetics Corporation (USA). IRAK4-gene expression was assessed with qRT-PCR.
Results
Whole exome sequencing analysis revealed a heterozygous variant in the patient: c.823delT (p.S275fs*13) in IRAK-4 gene.
Conclusions
IRAK-4 should be considered among patients with unclassified primary immunodeficiency. The diagnosis is confirmed by IRAK-4 gene sequencing. Clinical outcome improves with age. Prophylactic treatment with immunoglobulins is recommended until the teenage years.