P23 First reported case of an interleukin-2 receptor ß deficiency in an infant born to non-consanguineous parents, presenting with failure to thrive and enteropathy

Introduction Failure to thrive is not an uncommon paediatric presentation with multiple, often easily treatable, aetiologies. Immune dysfunction is a rare cause which often manifests with a combination of inflammatory and infectious pathology. Aim We present a rare cause of immune deficiency, the first reported case attributable to this genetic abnormality in the absence of consanguinity, presenting with immune mediated enteropathy. Method A five-month-old female presenting with bronchiolitis symptoms, was found to be failing to thrive. Her weight was on the 0.4th centile, gaining just 200 g in the preceding eight weeks. The first born to non-consanguineous parents of Pakistani descent, she was born at 39 weeks’ gestation weighing 2.52 kg. There was no significant family history and she had breastfed successfully for the first three months, growing along the 9th centile, and meeting developmental milestones. By seven months she was 1 kg below the 0.4th centile, weighing the same as at three months. Bottle refusal and a failure to wean to solids accompanied chronic diarrhoea, oral and perianal inflammation, and eczematous dermatitis. Amino acid nasogastric feeds resulted in a small weight gain, but no relief of systemic symptoms. Developmental delay and soft dysmorphic features were apparent, and she developed recurrent fevers, polyarticular swelling affecting knees and joints of the hands and feet, widespread lymphadenopathy, and chronic bilateral uveitis. Results Double negative T cell levels were elevated, inflammatory markers and liver enzymes were persistently high and cytomegalovirus (CMV) IgG was positive. Hypergammaglobulinaemia and numerous autoantibodies were demonstrated. Faecal calprotectin was markedly raised, and endoscopy revealed nonspecific acute on chronic inflammation of the duodenum and stomach. By 12 months of age, total parenteral nutrition and pulsed methylprednisolone, followed by oral prednisolone had been started. Symptoms improved, she began to gain weight and make developmental progress. Full genome sequencing and parental genetic analysis, identified an autosomal recessive interleukin-2 receptor s (IL2RB) mutation, giving a diagnosis of IL2RB deficiency. The patient is now recovering following haematopoietic stem cell transplantation, with the aim of definitive cure. Conclusion Interleukin-2 is involved in building protection against autoimmune disease by stimulating T-cell differentiation. Genetic mutations in its receptor are exceptionally rare, with only four homozygous defects identified in seven infants, one neonate, and two fetuses, all conceived to consanguineous marriage partners. Common clinical manifestations amongst the seven surviving the neonatal period reflect the underlying immune dysregulation with enteropathy, arthritis, uveitis, dermatitis and hypergammaglobulinaemia, together with a susceptibility to respiratory and herpesvirus infections. Inflammatory features were prominent in this case but she went on to develop symptoms of CMV illustrating the conundrum of managing inflammation with underlying immunosuppression. Failure to thrive, diarrhoea, eczema and recurrent viral infections are not uncommon in paediatrics. However, when rare aetiology is responsible, the journey from presentation to diagnosis can be long. The time from presentation to referral for definitive treatment was remarkably quick in this case. This is testament to the exceptional collaborative multidisciplinary working across sub specialities, leading to a prompt diagnosis and definitive management.