Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye.

Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients' long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers.

Allergic reactions to enzyme replacement therapy in children with lysosomal storage diseases and their management.

OBJECTIVES: Human recombinant enzyme replacement therapy, given to compensate for genetic enzyme deficiency in lysosomal storage diseases, delays the progression of the disease and improves the quality of life. However, enzyme replacement therapy may cause hypersensitivity reactions. Within the scope of this research, we aimed to elucidate the frequency and clinical features of hypersensitivity reactions against enzyme replacement therapy in children with lysosomal storage diseases and clarify the management of these reactions. METHODS: Medical records of pediatric patients with lysosomal storage disease and receiving enzyme replacement therapy were retrospectively reviewed, and patients who experienced allergic reactions were included in the study. The demographic characteristics of the patients, their diagnosis, the responsible enzyme, the time at which the reaction started and at what dose, the signs and symptoms associated with the reaction, diagnostic tests, the management of the reaction, and the protocol applied for the maintenance of enzyme replacement therapy after the reaction were recorded. RESULTS: Hypersensitivity reactions developed in 18 of 71 patients (25.3 %) who received enzyme replacement therapy. The most common cutaneous findings were observed. Anaphylaxis developed in 6 of 18 patients. Patients who experienced recurrent hypersensitivity reactions with premedication or a slower infusion rate, those with positive skin test results, and patients who developed anaphylaxis were given enzyme replacement therapy with desensitization. CONCLUSIONS: HSR may develop during enzyme replacement therapy, which are vital in lysosomal storage diseases, and discontinuation of enzyme replacement therapy is a significant loss for patients with metabolic disorders. These reactions can be treated with premedication and long-term infusions, but some patients may require desensitization protocols for continued treatment.

A Rare Autoimmune Disease Detected in the Differential Diagnosis of Immunodeficiency: Histiocytosis-lymphadenopathy Plus Syndrome.

Mutations in the SLC29A3 gene cause histiocytosis-lymphadenopathy plus (H) syndrome, a rare autosomal recessive genetic condition that affects numerous systems. We present a 7-year-old Syrian patient with pericardial effusion whose acute phase reactants did not decrease despite treatment. In order to emphasize the variety and raise awareness of H syndrome in the hopes of achieving an early diagnosis and appropriate treatment, molecular investigation of SLC29A3-related disorders is crucial. H syndrome is an uncommon genetic condition with a broad spectrum of phenotypes. Therefore, early genetic testing is essential for the accurate diagnosis of patients. Doctors should be aware of this condition and its symptoms and consider autoimmune diseases as a possible alternative diagnosis in patients with suspected immunodeficiency.

Disordered bone metabolism in hereditary spherocytosis patients.

Aim: This study was planned to evaluate bone health in patients with hereditary spherocytosis.Materials and methods: In this prospective study, a total of 30 hereditary spherocytosis patients which followed in the Pediatric Hematology and Oncology Department of KSU Medical Faculty and 30 patients for control group were included. Patient and control group were chosen equal in age and sex. Hemogram and biochemical tests (serum calcium, phosphorus, alkaline phosphatase, parathormone, vitamin D) and osteocalcin were studied from the patient and control groups. Also DXA examination was performed in the patient group.Results: There was a significant difference in hemogram parameters between the two groups due to hemolytic anemia in hereditary spherocytosis patients. In the patient group, osteocalcin was 6.88 ± 4.35 ng/ml, vitamin D was 17.74 ± 7.76 ng/ml and in the control group osteocalcin was 11.93 ± 8.92 ng/ml, vitamin D was 24.04 ± 11.70 ng/ml. There was a statistically significant difference between the vitamin D and osteocalcin levels of the two groups (p = 0.017 and 0.008, respectively). Bone density was assessed in the patient group. In patients DXA results showed lower Z-scores then the normal population according to age and sex.Conclusion: Hereditary spherocytosis patients should be followed closely in terms of development, puberty, bone health as they are in other hemolytic anemias. Nutritional recommendations, vitamin D supplementation, physical activity should be advised to protect bone health.