Spectrum of Primary Immune Regulatory Disorders in Children in a Highly Consanguineous Population: Report from a National Registry.

backgroundPrimary Immune Regulatory Disorders (PIRDs) are caused by genetic defects resulting in diverse clinical manifestations. We aimed to present the spectrum of PIRDs in children in Kuwait.

methodsThe data was obtained from the Kuwait National Primary Immunodeficiency Disorders Registry (KNPIDR), and the patients were followed prospectively.

results59 patients with PIRDs, constituting 14% of all patients registered in the KNPIDR, were included in this study. Most of the patients belonged to familial hemophagocytic lymphohistiocytosis syndromes (42.4%), followed by regulatory T cell defects subcategories (15.3%). The median ages at the onset of symptoms and diagnosis were 4 and 18 months, respectively. Parental consanguinity was documented in 88.1% of cases while family history of PIRDs in 45.7%. The most common clinical features were lymphoproliferation, hematologic manifestations, and infections, affecting 71.2%, 67.8%, and 47.5%, respectively. Genetic diagnosis was reached in 84.9% of the tested patients and the most common genes affected were STXBP2 followed by PRF1 and LYST. Most patients (88.8%) had autosomal recessive disease. 35.6% of the patients underwent hematopoietic stem cell transplantation and a similar percentage received immunosuppressive and/or immunomodulating therapies. There was a total of 21 deaths (35.6%) with a median age at death of 36 months while the median time from diagnosis to death was 5 months.

conclusionsPIRDs are heterogenous group of disorders with complex disease phenotypes. Genetic testing should be done as soon as possible when these diseases are suspected since early diagnosis is crucial for proper therapeutic interventions.