Newborn screening for severe combined immunodeficiency: The results of the first pilot TREC and KREC study in Ukraine with involving of 10,350 neonates.

Severe combined immunodeficiency (SCID) is a group of inborn errors of immunity (IEI) characterized by severe T- and/or B-lymphopenia. At birth, there are usually no clinical signs of the disease, but in the first year of life, often in the first months the disease manifests with severe infections. Timely diagnosis and treatment play a crucial role in patient survival. In Ukraine, the expansion of hemostatic stem cell transplantation and the development of a registry of bone marrow donors in the last few years have created opportunities for early correction of IEI and improving the quality and life expectancy of children with SCID. For the first time in Ukraine, we initiated a pilot study on newborn screening for severe combined immunodeficiency and T-cell lymphopenia by determining T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs). The analysis of TREC and KREC was performed by real-time polymerase chain reaction (RT-PCR) followed by analysis of melting curves in neonatal dry blood spots (DBS). The DBS samples were collected between May 2020 and January 2022. In total, 10,350 newborns were screened. Sixty-five blood DNA samples were used for control: 25 from patients with ataxia-telangiectasia, 37 - from patients with Nijmegen breakage syndrome, 1 - with X-linked agammaglobulinemia, 2 - with SCID (JAK3 deficiency and DCLRE1C deficiency). Retest from the first DBS was provided in 5.8% of patients. New sample test was needed in 73 (0.7%) of newborns. Referral to confirm or rule out the diagnosis was used in 3 cases, including one urgent abnormal value. CID (TlowB+NK+) was confirmed in a patient with the urgent abnormal value. The results of a pilot study in Ukraine are compared to other studies (the referral rate 1: 3,450). Approbation of the method on DNA samples of children with ataxia-telangiectasia and Nijmegen syndrome showed a high sensitivity of TRECs (a total of 95.2% with cut-off 2000 copies per 106 cells) for the detection of these diseases. Thus, the tested method has shown its effectiveness for the detection of T- and B-lymphopenia and can be used for implementation of newborn screening for SCID in Ukraine.

The association between vitamin D deficiency and metabolic syndrome in Ukrainian adolescents with overweight and obesity

Purpose@#This work aims to determine the association between vitamin D deficiency and metabolic syndrome in overweight and obese adolescents from Ukraine. @*Methods@#Anthropometric measurements were taken and general and biochemical examinations were performed on 136 obese and overweight adolescents and 60 adolescents with normal body weight. The vitamin D status was determined using 25-hydroxyvitamin D (25(OH)D) (calcidiol) levels in blood serum. To establish the factors influencing vitamin D status, the subjects were asked to answer a questionnaire and 2007 International Diabetes Federation diagnostic criteria were used to determine the incidence of metabolic syndrome. All research results were processed statistically. @*Results@#A calcidiol sufficiency level was found in 3.9% of obese adolescents and 6.7% of overweight adolescents. Metabolic syndrome was found in 64.4% of obese adolescents with vitamin D deficiency, and in 26.2% of overweight adolescents. Factors associated with an increased risk of developing vitamin D deficiency in adolescents with metabolic syndrome included male sex (p=0.042), low income per family member (p=0.040), daily milk consumption of up to 1 cup per day (p=0.001), physical activity (p=0.001), duration of outdoor stays (p=0.001), and passive rest in front of a computer or television (p=0.001). Adolescents with metabolic syndrome were found predominance of body mass index (p<0.001), waist circumference (p<0.001), fasting blood glucose level (Р<0.001), and decreased calcidiol level (p=0.022). Among metabolic syndrome components, vitamin D deficiency was strongly associated with waist circumference and increased fasting blood glucose (p<0.05). @*Conclusion@#Vitamin D deficiency is prevalent in overweight and obese adolescents from Ukraine. Vitamin D deficiency is associated with metabolic syndrome criteria in overweight and obese adolescents.

TREC/KREC levels in children with ataxia-telangiectasia.

The aim of the study was to determine the TREC/KREC levels in the patients diagnosed with ataxia-telangiectasia (AT) and to establish their informative value for early diagnosis of this pathology. TRECs and KREC assay was performed using real-time polymerase chain reaction on the DNA of 25 patients diagnosed with AT aged 3 to 14 years and of 173 healthy individuals of the control group aged 1 to 12 years. Clinical and laboratory characteristics of patients were ascertained using their medical records. In the patients with AT, the mean level of TRECs was 542.84 per 106 cells, ranging from 4 to 4720, while mean level of KRECs was 1317.64 per 106 cells, ranging from 146 to 9300. In 84% of the patients, TREC levels were less than 1000, which was significantly lower than in the control group, while KREC levels were reduced in 48% of the patients. A correlation was found between the levels of TREC and the absolute values of CD4 (r = 0.5455). Measurement of TREC/KREC levels opens new opportunities for early AT detection in children as a part of the newborn screening. Reduced time to diagnosis will allow to carry out timely in-depth immunological and genetic testing, prevent the development of severe infections, and improve quality of life.

Relation of carbohydrate exchange markers with vitamin D status in adolescents with overweight and obesity.

INTRODUCTION: In the case of obesity and excessive body weight, the deficiency of vitamin D increases, which significantly impairs metabolic processes in the body, especially fatty and carbohydrate metabolism. Vitamin D metabolites affect insulin sensitivity of cells. THE AIM OF THE STUDY: was to determine the relationship between vitamin D and carbohydrate metabolism in adolescents with excessive body weight and obesi-ty. MATERIAL AND METHODS: 139 adolescents were examined. The mean age of children was 15.5 ±2.3 years. 65 adolescents with excessive weight and 74 obesity teenagers were examined. Parameters that were determined in all children included: undertaking anthropometric measurements, general examinations, biochemical parameters, including carbohydrate metabolism: fasting glucose, insulin, oral glucose tolerant test, measuring the homeostasis model assessment for insulin resistance, blood pressure measurement and determination of vitamin D status. RESULTS: The features of changes carbohydrate metabolism markers in adolescents with overweight and obesity, depending on the level of serum 25(OH)D, have been established. Correlations between vitamin D status and markers of carbohydrate metabolism such as basal insulin level (p = 0.000) and HOMA-IR index (p = 0.000) and anthropometric indices: body mass index (p = 0.000), waist circumference (p = 0.000) and hip circumference (p = 0.001), waist-hip ratio (p = 0.000), waist-to-height ratio (p = 0.000) have been determined. CONCLUSIONS: The study has established prognostically significant biochemical (basal insulin), and anthropometric (body mass index, waist circumfer-ence, waist-hip ratio, and waist-to-height ratio) markers resulting in vitamin D deficiency development in children with excessive body weight and obesity.