Background: Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS‐CoV‐2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID‐19 outcomes.Methods: We studied 34 IEI patients (19M/15F, 12 [min: 0.6‐max: 43] years) from six centers. We diagnosed COVID‐19 infection by finding a positive SARS‐CoV‐2 PCR test (n = 25) and/or a lung tomography scoring (CORADS) ≥4 (n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass.Results: Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID‐related death (OR: 2.630, 95% CI; 1.198–5.776, p < .001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin‐T, ferritin, and total‐lung‐score (p = .020, p = .003, p = .014, p = .013, p = .020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG (p = .012, p = .022, p = .011; respectively).Conclusion: Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID‐19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS‐Cov‐2 therapy trials.

Schimke Immuno-Osseous Dysplasia (SIOD) (MIM:242900) is an ultra-rare autosomal recessive pan-ethnic pleiotropic disease. Typical findings of this syndrome are steroid-resistant nephrotic syndrome, cellular immunodeficiency and spondyloepiphyseal dysplasia and facial dysmorphism. Biallelic variants in the SMARCAL1 gene cause SIOD. The five-and-half-year-old female patient was evaluated because of short stature, dysmorphism, hypercalcemia, hypophosphatemia and elevated FSH levels. Karyotype analysis and array-CGH testing were normal. Clinical Exome Sequencing was performed via next-generation sequencing to analyze genes associated with hypophosphatemia. No pathogenic variant was detected. The subsequent detection of proteinuria during her follow-up for cross-fused ectopic left kidney ultimately facilitated the diagnosis of SIOD, although no obvious spondyloepiphyseal dysplasia was detected. Re-analysis of CES revealed a novel homozygous c.2422_2427+9delinsA pathogenic variant in the SMARCAL1. One hundred twenty-five SIOD cases from 38 literature reporting SMARCAL1 gene pathogenic variants were reviewed to investigate whether hypercalcemia, hypophosphatemia and elevated FSH levels had been previously reported in SIOD patients. This review revealed that this was the first time these findings had been reported in a SIOD patient. This report expands not only the phenotypic but also genotypic spectrum of SIOD.

Juvenile idiopathic arthritis (JIA) is a common, chronic and inflammatory rheumatological disease of childhood. The disease can affect all synovial joints in the body. Temporomandibular joints (TMJs) are important areas of involvement in JIA, which are frequently involved but often not noticed because the involvement is usually asymptomatic. The aim of this study is to determine the frequency and risk factors of TMJ joint involvement in juvenile idiopathic arthritis patients admitted to our clinic, and to guide for early diagnosis and treatment. Patients who applied to this study with the diagnosis of JIA between January 2014 and May 2017 at Pediatric Rheumatology Clinic, were followed up regularly in our clinic, had a accessible medical history, and a rheumatology polyclinic record. Patients with contrast-enhanced TMJ Magnetic Resonance Imaging (MRI) taken and reported by the radiologist were included. TMJ involvement was detected in 51.2% of the 41 patients included in the study. It was found that 71.5% of the patients with TMJ involvement were asymptomatic and 71.5% of the patients had chronic involvement. When the patients with and without TMJ involvement were compared according to the contrast-enhanced TMJ MRI results; In the patient group with involvement, the polyarticular onset subtype was seen at a higher rate (p = 0.005), the age of onset was earlier (p = 0.003), the disease duration was longer (p = 0.037), more joints were involved (p = 0.005), the ESR values ​​were higher (p = 0.0001), and the treatment compliance and treatment responses of the patients in this group were worse (p = 0.001, p = 0.0001). TMJ involvement is common in JIA patients and can occur at any stage of the disease. It is often asymptomatic and progresses insidiously, leading to chronic and degenerative changes in the mandible at an early stage. Due to its asymptomatic nature, the insidious progression, and the risk of causing chronic, irreversible sequelae, it is crucial to screen high-risk JIA patients regularly with contrast-enhanced TMJ MRI, which remains the gold standard method. While specific risk factors are difficult to pinpoint, some factors may increase the likelihood of TMJ involvement. To better identify these high-risk patients and determine which individuals require regular screening, larger-scale and multicenter studies are essential.

The Janus kinase/signal transducer and activator of transcription signaling pathway orchestrates crucial aspects of immune regulation, including cytokine signaling, cellular proliferation, differentiation, and apoptosis. Dysregulation of this pathway due to gain- or loss-of-function mutations significantly contributes to the development of inborn errors of immunity and various immune-mediated disorders. Understanding the molecular basis of these abnormalities is fundamental for enhancing diagnostic precision and developing targeted therapies. A bibliographic search was conducted in PubMed and MEDLINE for articles published up to June 2025. The review offers a comprehensive overview of the structural and functional features of JAK/STAT family proteins, the intrinsic regulatory mechanisms, and the immunopathological consequences of STAT1, STAT3, and STAT6 GOF mutations. Recent clinical advances, particularly the therapeutic impact of JAK inhibitors and emerging novel molecules, are critically discussed, emphasizing the integration of molecular insights into clinical practice. Advances in the molecular characterization of JAK/STAT pathway dysregulation have opened new avenues for precision medicine approaches. While JAKinibs have shown promising outcomes, further research is needed to optimize therapeutic strategies, identify predictive biomarkers, and refine patient selection to maximize clinical benefits. Novel targeted therapies can reshape the management of JAK/STAT-related diseases in the coming years.

Objective: Prolidase deficiency is a metabolic and immunological disorder that is inherited in an autosomal recessive manner. In prolidase deficiency, a broad spectrum of differences is observed in patients, ranging from asymptomatic to multisystem involvement. There is scarce information in the literature on the atypical features and immunophenotypes of this disease. Aim of this study is to present 4 new cases to provide information on the rare features of the disease and to raise awareness. Materials and Methods: This study included 4 female patients with prolidase deficiency. Their demographic, clinical, and immunologic characteristics were obtained from their medical records. Results: There were 4 female patients (P1-P4), with a mean age of 18.5 years (min-max: 10-29) and a mean age of symptom onset of 6.9 years (min-max: 0.04-27). The main presenting complaints of the patients were skin lesions (100%), dysmorphic features (100%), neurodevelopmental delay (100%), frequent infections (100%), and prolonged diarrhea (50%). P2 had diffuse large B-cell lymphoma, resulting in early death. Interestingly, P1 and P2 experienced opportunistic infections such as cytomegalovirus, Epstein-Barr virus, and Pneumocystis jirovecii. Three patients (75%) had lymphopenia. Two patients had elevated IgE levels. Lymphocyte subgroup analysis showed an inverted CD4/CD8 ratio in all patients. In patients P1 and P2, the percentages of naive T cells and recent thymic emigrants were reduced, suggesting combined immune deficiency at the time of diagnosis. CD19+ B cells were also low in P1 and P2. Metabolic evaluations revealed low prolidase enzyme activity in P1 and P2. Conclusion: Beyond the well-known classical dermatological findings, the presence of recurrent opportunistic infections, gastrointestinal involvement, malignancy, and flow cytometry findings suggestive of combined immunodeficiency indicate that the diagnosis of prolidase deficiency may be underestimated. Knowing the atypical and rare presentations will facilitate diagnosis and treatment of affected patients. Cite this article as: Yalcin Gungoren E, Meric Z, Pinar Sefer A, et al. Beyond dermatological findings: Multisystem involvement in prolidase deficiency – A report of four cases. Turk Arch Pediatr. 2025;60(1): 48-56.

Background: In this study, we present our experience with bicaval, dual-lumen, venovenous extracorporeal membrane oxygenation in pediatric patients with severe respiratory failure. Methods: Between September 2015 and May 2019, a total of nine pediatric patients (7 males, 2 females; median age 3.1 years; range, 0.3 to 7.4 years) hospitalized in the pediatric intensive care unit due to severe respiratory failure who were cannulated using a bicaval, dual-lumen, venovenous catheter were retrospectively analyzed. Patient demographics, cannulation details, complication of catheter use, and outcomes were recorded. Results: The median duration of extracorporeal membrane oxygenation support was nine (range, 2 to 32) days. One patient required conversion to venoarterial extracorporeal membrane oxygenation and one patient required conversion to conventional double-cannulated venovenous extracorporeal membrane oxygenation. Of the patients, 33% suffered from bleeding complications. There were no cannula- or circuit-related complications. Adequate oxygenation and flow were obtained in all patients, except one. No mortalities were directly associated with the cannulation strategy used. Conclusion: The bicaval, dual-lumen cannula can be safely used in pediatric patients with minimal complication rates and is our preferred method for venovenous extracorporeal membrane oxygenation support.