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OBJECTIVE: This study aimed to provide a comprehensive overview of the clinical features, laboratory and screening results, treatment options, and outcomes of patients with type 1 interferonopathy. Our secondary goal was to identify the predictors of long-term morbidities or fatalities. METHODS: We included children with genetically confirmed type 1 interferonopathies, with a follow-up duration of > 1 year. Data were obtained retrospectively from medical records. RESULTS: Of the 40 eligible patients for the study, 52.5% were female, with a median age of disease onset of 1.5 years (0.1-13.2). They were diagnosed at an average age of 6.8 ± 4.6 years. Aicardi-Goutières Syndrome was the most common diagnosis (n=15; 37.5%). The central nervous system was the most frequently affected system (n=27; 67.5%). Janus kinase inhibitors were administered to 17 (42.5%) patients. Twenty-five patients (62.5%) developed at least one permanent morbidity or died during follow-up; thus, they were included in the poor-outcome group. While younger age at disease onset, intracranial calcification (ICC), and lack of chilblains and elevated acute phase reactants (APRs) were significant in univariate logistic regression analysis, only ICC on MRI at admission (aOR, 19.69; 95% C.I.: 1.08-359.05, p=0.04) was found to be a significant predictor of poor outcomes in multivariate logistic regression analysis. CONCLUSION: For the first time, we evaluated the predictors of poor outcomes in patients with type 1 interferonopathy with a broad spectrum of subtypes. Furthermore, our study's unique patient characteristics can provide valuable insights into these extremely rare conditions.
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BACKGROUND: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented. METHODS: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control. RESULTS: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation. CONCLUSION: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life.