[Dynamics of indicators of vitamin D status in children with cystic fibrosis of the Moscow region for 2016-2018].

Vitamin D deficiency is widespread in patients with cystic fibrosis (CF). From 2016 to 2018, prophylactic doses of vitamin D were prescribed for the patients of the Russian cystic fibrosis Center in accordance with the National cystic fibrosis consensus and they were informed about the role of vitamin D deficiency. The aim of the study was to conduct a comparative analysis of the frequency of deficiency and insufficiency of vitamin D in children with CF of different ages in Moscow region in 2016 and 2018. Material and methods. The study involved 115 patients with CF at the age of 0-18 in 2016 and 211 children of the same age in 2018. All children underwent determination of 25(OH)D in blood serum by ELISA. Results and discussion. The frequency of vitamin D deficiency and insufficiency [25(OH)D level <30 ng/ml] in CF patients in 2016 was 64.3%, and in 2018 - 48.7%. Among children of 0-3 years normal serum 25(OH)D levels (>30 ng/ml) were registered in 62.5% in 2016 and in 62.2% in 2018, in children of 4-11 years - 28.8% in 2016 and 58.1% in 2018, among adolescents (11-18 years) - 11.8 and 30.2%, respectively. Conclusion. Comparative analysis showed a positive dynamics in reducing the proportion of CF patients with vitamin D deficiency and insufficiency against the background of continuous use of prophylactic doses of cholecalciferol and educational work for the period from 2016 to 2018. However, in a significant proportion of patients (48.7%), vitamin D level did not reach the norm in 2018 that requires the correction of preventive doses and increase in patient compliance.

[Dietary intake of children with cystic fibrosis].

The high incidence of nutritional deficiency in cystic fibrosis continues to be an urgent problem in pediatrics. This is due to the multifactorial nature of these violations, one of which is the lack of effectiveness of nutritional correction. The aim of the research was to assess the actual diet of children and adolescents suffering from cystic fibrosis in order to develop an algorithm for individual approaches to correcting nutritional status. MATERIAL AND METHODS: 150 children (boys - 85, girls - 65) aged 1 year to 18 years (average age 6.4±5.2 years) with a confirmed diagnosis of cystic fibrosis have been examined. Depending on age, the children were divided into groups: the 1st group consisted of 40 children from 1 year to 2 years (average age 1.9±0.7 years); 2nd group - from 3 to 5 years (n=41, 4.4±1.0 years); 3rd group - from 6 to 9 years (n=43, 7.7±1.1 years); 4th group - from 10 to 18 years old (n=26, 13.1±2.5). The actual nutrition was evaluated by questionnaire for 3 days, including one day off. Body mass, height have been measured, and body mass index (BMI) have been calculated. RESULTS AND DISCUSSION: Only children of the first three years of life had an optimal diet for this disease in terms of energy value. At the age of 3 years and older, the deficit of energy intake increased, reaching 32% of the individual requirement in adolescence (10-18 years). The structure of nutrition revealed an imbalance of the main nutrients in the direction of the predominance of the lipid component (more than 40% of the energy value) and increased intake of saturated fatty acids, with a reduced proportion of protein and carbohydrates. There was a lack of dietary intake of a number of vitamins (C, B1, B2, A, E, D) and mineral substances (iron, potassium). CONCLUSION: The study showed the need for an individual approach to the correction of diet energy value and macronutrient intake in children with cystic fibrosis.

Spectrum of CFTR mutations in Chechen cystic fibrosis patients: high frequency of c.1545_1546delTA (p.Tyr515X; 1677delTA) and c.274G>A (p.Glu92Lys, E92K) mutations in North Caucasus.

BACKGROUND: Cystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease caused by pathogenic variants (henceforward mutations) in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The spectrum and frequencies of CFTR mutations vary among different populations. Characterization of the specific distribution of CFTR mutations can be used to optimize genetic counseling, foster reproductive choices, and facilitate the introduction of mutation-specific therapies. Chechens are a distinct Caucasian ethnic group of the Nakh peoples that originated from the North Caucasus. Chechens are one of the oldest ethnic groups in the Caucasus, the sixth largest ethnic group in the Russian Federation (RF), and constitute the majority population of the Chechen Republic (Chechnya). The spectrum of CFTR mutations in a representative cohort of Chechen CF patients and healthy individuals was analyzed. METHODS: Molecular genetic analysis of 34 CFTR mutations (representing approx. 80-85% of mutations in multiethnic CF populations of the RF) was performed in 32 CF patients from 31 unrelated Chechen families living in Chechnya. One hundred randomly chosen healthy Chechens were analyzed for the 15 most common "Russian" mutations. The clinical symptoms in Chechen CF patients with different CFTR genotypes were investigated. RESULTS: High frequencies of c.1545_1546delTA (p.Tyr515X; 1677delTA) (52 out of 64 CFTR alleles tested; 81.3%) and c.274G > A (p.Glu92Lys, E92K) (8/64, 12.5%) mutations were found. Twenty patients were homozygous for the c.1545_1546delTA mutation, and eight were compound heterozygous for the c.1545_1546delTA and c.274G > A mutations. Three carriers of the c.1545_1546delTA mutation were also found in the cohort of 100 apparently healthy Chechens (frequency - 0.015). The c.1545_1546delTA and c.274G > A mutations are linked to the same haplotype (22-7-16-13) of intragenic Short Tandem Repeat markers, i.e., IVS1CA, IVS6aGATT, IVS8CA, and IVS17bCA. CONCLUSIONS: The distribution of CFTR mutations in the Chechen CF population is unique regarding the high frequency of mutations c.1545_1546delTA and c.274G > A (more than 90% of the mutant alleles). The c.274G > A mutation is associated with a less severe course of CF than that observed in c.1545_1546delTA homozygotes. Testing for these two variants can be proposed as the first step of CF DNA diagnosis in the Chechen population.

High prevalence of W1282x mutation in cystic fibrosis patients from Karachay-Cherkessia.

Cystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease. The spectrum and frequency of CFTR mutations vary significantly in different populations and ethnic groups. A genetic epidemiological study was conducted in the indigenous ethnic group of people known as the Karachais. They live in the Republic of Karachay-Cherkessia, which lies in the northwest of Russia's North Caucasus region. Karachai's are Turkic-speaking and consist of 194 thousand people (approximately 40% of the population of the Republic). Molecular genetic analysis was performed in 10 unrelated Karachai families with CF patients from three districts in the Republic. A high frequency of W1282X mutation was found (18 of 20 mutant alleles): eight patients were homozygous for the W1282X mutation, and two were compound heterozygous (the second alleles were R1066C and R709X). Analysis for 13 common CF mutations in the sample of 142 healthy Karachais identified two 1677delTA and two W1282X mutation carriers. Thus, the most common CFTR mutation, F508del, was not detected among the CF patients or in healthy Karachais. The most frequent mutation among Karachai patients is W1282X (90%). Its frequency in healthy Karachais is approximately 0.007. Haplotype analysis using the CFTR intragene DNA markers IVS1CA, IVS6aGATT, IVS8CA and IVS17bCA showed that the origins of the W1282X mutation in Karachay-Cherkessia and the Eastern European part of Russia are different.