This article presents the first reported familial case of 17q12 recurrent deletion syndrome in Russia, involving a female patient with diabetes and her daughter diagnosed with atypical autism without intellectual disability. A comprehensive analysis of the molecular genetic features and intrafamilial variability of clinical manifestations was performed. In addition, clinical, laboratory, and instrumental findings were compared with those observed in a classical case of maturity-onset diabetes of the young type 5 (MODY5). Furthermore, the disease course associated with other genetic alterations affecting the 17q12 region, including 17q12 microduplications and various pathogenic variants of the HNF1B gene, was comparatively evaluated. Given the orphan nature of this condition, the present report adds to the limited existing data on the clinical and genetic characteristics of 17q12 recurrent deletion syndrome.

Maturity-onset diabetes of the young type 3 (MODY3) disorder is characterized by an autosomal dominant type of inheritance and highly heterogeneous clinical phenotype influenced by type and position of mutation in the HNF1A gene. We reprogrammed dermal fibroblasts derived from a patient with MODY3 carrying a heterozygous mutation in the site encoding the transactivation domain of the HNF1A protein (с. 864delGinsCC, p.Gly292ArgfsTer25) into iPSCs using transfection with self-replicating RNA vector. Obtained iPSCs (ERCi004‑A line) proliferate in dense monolayer cell colonies, have a normal karyotype (46,XX), express pluripotency markers (OCT4, SOX2, TRA-1-60). The functional pluripotency of iPSCs was confirmed by their ability to form embryoid bodies and differentiate into the three germ layers (ecto-, endo-, and mesoderm). Sanger sequencing of iPSCs confirmed the presence of pathogenic heterozygous mutation in the HNF1A gene. This cell line could be useful to modeling of MODY3 pathology to improve understanding of the mechanism of the transactivation domain mutation, as well as a potential source for autologous cell-based therapy.

IntroductionHNF4A-MODY is a rare subtype of MODY in children that requires treatment. The clinical features of children with HNF4A-MODY are limited. Adult patients with HNF4A-MODY are treated with insulin, diet, oral antidiabetic drugs, and incretin drugs. Our cross-sectional study presents the clinical features of 15 probands with genetically confirmed HNF4A-MODY from the pediatric registry of MODY in Russia.Materials and methodsThis study presents the genetic, clinical, and laboratory characteristics of 15 children with HNF4A-MODY in the Russian population.ResultsThe frequency of HNF4A-MODY was 1.8%, 95% CI [1.0, 3.0] among all pediatric MODY cases (n = 15/807) in Russia. The median age at diagnosis was 12.8 years [12.1, 14.0]. Hyperglycemia was diagnosed incidentally in 71.5% of cases. Glycated hemoglobin (HbA1c) was 8.0% [7.0, 9.2]. At birth, macrosomia was present in 35.7% of patients and hypoglycemia in 7%. Family history was positive in 57.1%, with DM diagnosed in first-degree relatives at age 29 [27.3, 32.8] years in 50% of cases, which was significantly different from the age of DM diagnosis in their children (p < 0.05).DiscussionWe examined patients with HNF4A-MODY with a duration of 1.2 [0.8, 1.9] years. The degree of hyperglycemia in all patients met the diagnostic criteria for DM. Molecular genetic testing revealed a high percentage of deletions and nonsense variants (28.5% each). 64.5% of patients were prescribed drug therapy (21% insulin, 43% metformin) at the onset of diabetes. Forty-three percent of patients were transferred successfully to sulfonylurea therapy (including patients with complete insulin withdrawal) following genetic testing and HNF4A-MODY verification. The attempt to switch from insulin to sulfonylurea drugs was unsuccessful due to significant glycemic deterioration in one case.

Maturity-onset diabetes of the young type 10 (MODY10) is inherited in an autosomal dominant manner, characterized by islet cell dysfunction, impaired insulin synthesis and secretion. MODY10 is relatively rare, and is caused by a mutation of the 11p15.5 site on chromosome 11 encoding insulin. We obtained iPSCs (ERCi003‑A line) from dermal fibroblasts derived from a patient with MODY10 carrying a previously undescribed pathogenic heterozygous mutation in the INS gene (с.93С>G, p.C31W) into iPSCs using transfection with self-replicating RNA vector. iPSCs proliferate in dense monolayer cell colonies, have a normal karyotype (46,XY), express pluripotency markers (OCT4, SOX2, TRA-1-60). The functional pluripotency of iPSCs was confirmed by their ability to form embryoid bodies and differentiate into the three germ layers (ecto-, endo-, and mesoderm). Sanger sequencing of iPSCs confirmed the presence of pathogenic heterozygous mutation in the INS gene. This cell line could be useful to thoroughly modeling of MODY10 to improve clinical understanding of the disease.

Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic diabetes forms that are frequently misclassified as type 1 or type 2 diabetes due to overlapping phenotypic features. The true prevalence of MODY is likely substantially underestimated. As DNA-based diagnostics become increasingly accessible, an expanding number of novel genetic variants are being identified. Objectives: The aim of this study was to characterize the clinical and genetic features of patients carrying rare variants in the BLK, KLF11, PAX4, PDX1, and CEL genes, with attention to population-specific aspects, family history, and treatment outcomes. Methods: Targeted next-generation sequencing (NGS) using a custom-designed panel covering 27 genes implicated in MODY, neonatal diabetes, and related hereditary syndromes was performed on the Illumina NovaSeq 6000 platform (Illumina). Results: We identified 21 variants in five genes associated with rare MODY subtypes among 24 unrelated patients. MODY9 was diagnosed in two unrelated patients of Russian ethnicity harboring an identical heterozygous missense mutation in exon 5 of the PAX4 gene (HG38, chr7:127615049G>A, c.191C>T, p.Thr64Ile), which has not been previously described in patients with diabetes. MODY11 was diagnosed in a patient carrying the c.773-1G>A variant in the BLK gene. A patient with a de novo c.40_41dupGC (p.Val15Glnfs*41) variant in the KLF11 gene was clinically diagnosed with type 1 diabetes. Conclusion: Our findings expand the current understanding of rare MODY subtypes and contribute to the growing body of evidence on the spectrum and frequency of potentially pathogenic variants in BLK, CEL, KLF11, PDX1, and PAX4 genes across ethnically diverse populations worldwide.

BACKGROUND: Type 1 diabetes mellitus (DM1) is a chronic autoimmune disease characterized by damage to insulin–producing cells of the pancreas, which eventually leads to the need for insulin replacement therapy. The clinical picture of DM1 is heterogeneous: the onset of the disease at an early age is characterized by a more acute manifestation and rapid depletion of residual insulin secretion. Variations of HLA genes can probably determine the clinical features of the course of DM1. To date, age-related features of HLA genes have been established in various populations, at the same time, such data are not available in the Russian population.AIM: To study the effect of HLA genes on predisposition to DM1 in preschool age.MATERIALS AND METHODS: A single-center, one-stage study, including data from 885 children (1 year — 18 years old) with previously diagnosed DM1 who are on intensified insulin therapy. The study participants’re divided into two groups: a group with a manifestation of DM1 <7 years and a group with a manifestation of DM1 ≥7 years. The age of diagnosis of DM1, SDS body mass index, glycated hemoglobin (HbA1c) and C-peptide levels, specific islet autoantibodies glutamate decarboxylase (GADA), tyrosine phosphase (IA-2A), zinc transporter (ZnT8A), HLA genes of classes I and II (NGS genotyping by high-performance sequencing) were analyzed.RESULTS: In the group with manifestations of DM1 <7 years, lower levels of C-peptide’re detected (0 vs. 0.3 ng/ml, p<0.001), AT GAD was less often determined (48% vs. 67%, p=0.028), IA-2 (52% vs. 62%, p=0.014), ZnT8 (44% vs. 71%, p=0.002). There were no significant differences in the sex ratio, the level of HbA1c and SDS BMI. In the group with manifestations of DM1 <7 years, there was a high frequency of the most severe predisposing genotype DRB1*03-DQA1*05:01-DQB1*02:01 (DR3-DQ2)/DRB1*04-DQA1*03:01-DQB1*03:02 (DR4-DQ8) (27.5% vs 21.5%, p=0.039]) and a lower frequency of the protective haplotype DRB1*01-DQA1*01-DQB1*05:01 (19.1% vs. 24.9%, p=0.035). With respect to class I HLA genes, in the group with manifestation <7 years, there was a high frequency of predisposing haplotype A*24:02 (35.6% vs. 24.1%, p=0.002). Regardless of the age of onset and duration of the disease, the absence of residual C-peptide secretion (<0.1ng/ml) was associated with the presence of the predisposing haplotype DR4-DQ8 (65.7% vs. 60.8%, p=0.04) and B*18:01 (20.9% vs. 16.9%, p=0.026), and also with a lower frequency of tread haplotypes DRB1*15-DQA1*01:03-DQB1*06:03 or DRB1*15-DQA1*01:02-DQB1*06:02 (1.3% vs. 3.3%, p=0.047). The presence of IA-2A and ZnT8A was associated with the DR4-DQ8 haplotype (28.2% vs. 16.5%, p=0.037, and 33.3% vs. 15.4%, p=0.018, respectively). GADAs were associated with the predisposing haplotype DR3-DQ2 (55.0% vs. 34.5%, p=0.03).CONCLUSION: Predisposing and protective HLA haplotypes of class I and II associated with the manifestation of DM1 in preschool age and the reserve function of beta cells have been established in the Russian population. The relationship of the presence of islet AT with predisposing DR3/DR4 haplotypes is shown, which can determine various mechanisms of formation and course of the autoimmune process.

Despite significant progress in the treatment of T1DM in children, achieving target levels of carbohydrate metabolism in children remains one of the most difficult tasks. The influence of the psychosocial state of the family on the ability to achieve metabolic compensation is becoming increasingly clear. However, the study of social risk factors in families with children with T1DM and their impact on metabolic control remains clearly insufficient.The purpose of the study is to determine social risk factors (SR) that are most typical for families of children with type 1 diabetes mellitus (T1DM) in our country and to analyze their relationship with compensation for T1DM based on a survey of parents.MATERIALS AND METHODS: The study was conducted in endocrinology departments of children’s hospitals and departments of medical and social care of children’s clinics in 4 regions - Vologda, Tyumen, Chelyabinsk regions and Khanty-Mansi Autonomous Okrug.A total of 325 respondents took part in the study. 1 group — experience of T1DM in children >1 year and poor metabolic control (level of glycated hemoglobin ((HbA1c) >7.5%) — 195 hours; 2 gr. — experience of T1DM in children >1 year and good metabolic control (HbA1c <7.5%) — 60 people. An additional group consisted of 73 patients with <1 year of experience of T1DM in children, regardless of metabolic control, in order to analyze the prevalence of social risk factors already in the 1st year of diabetes.RESULTS: In the overall group, HbA1c was 9.1% (4.9–17%). The five most common SR factors were a low level of parental education (lack of higher or secondary education), lack of a permanent job, raising a child alone, lack of support from loved ones, and income below the subsistence level.1 group (192 people). Average HbA1c level 9.8% (7.5–17%). Among the HR factors that significantly influence HbA1c levels, the level of education of parents, single parenting of a child, low family income and the number of children in the family were identified. The number of influencing social risk factors also has a negative impact on metabolic control.2nd group. (60 people). HbA1с — 6.6% (5.3%–7.3%). The prevalence of SR factors was significantly lower than in the previous group. The differences were significant for lack of higher education, single parenting, and low family income.3 gr. (73 people). HbA1c — 9.3% (4.9–15.1%, which may be due to the duration of diabetes less than 3 months in some children. After 3 months, the HbA1c level was 7.9% (4.8–13.4%). The list of SR factors practically coincides in composition and frequency with those in families of group 1. Thus, social difficulties that are not resolved in a timely manner aggravate the situation of the family and negatively affect the compensation of carbohydrate metabolism.CONCLUSION. We have identified the most significant factors of SR in families with children with T1DM in the Russian Federation. The deterioration of social conditions in the family is a factor that negatively affects the level of control of T1DM and the development of complications in the future. As a result, families with children with T1DM, especially with chronic decompensation, need assessment of SD factors and support from social services.

GATA6 syndrome is a rare monogenic disorder caused by heterozygous variants in the gene GATA6, which controls the early embryonic differentiation of germ layers and the development of different organs. We present the results of the 7-year follow-up of a child with this syndrome as well as the following conditions: diabetes mellitus, exocrine pancreatic insufficiency, gallbladder atresia, and congenital heart disease (CHD). At birth, the patient was diagnosed with neonatal diabetes mellitus (NDM) associated with heart (mitral valve prolapse) and gastrointestinal abnormalities (gallbladder atresia). Diabetes remitted within weeks and relapsed at the age of 2. We identified a de novo variant of a 4-nucleotide deletion (c.1302+4_1302+7del), previously unreported in the literature, in the donor splicing site of exon 3 of the GATA6 gene in a heterozygous state. Screening for other possible components of GATA6 syndrome revealed exocrine pancreatic insufficiency, and pancreatic enzyme replacement therapy resulted in improved dyspeptic symptoms, and growth rates increased. In addition, the patient was diagnosed with autoimmune thyroiditis and progressive myopia.

BACKGROUND: MODY (maturity-onset diabetes of the young) is a rare monogenic form of diabetes mellitus, the gold standard of diagnosis is mutations detection in the genes responsible for the development of this form diabetes. Genetic test is expensive and takes a lot of time. The diagnostic criteria for MODY are well known. The development of clinical decision support system (CDSS) which allows physicians based on clinical data to determine who should have molecular genetic testing is relevant.AIM: Provided a retrospective analysis of clinical data of the patients with T1DM and MODY, from 0 to 18 years old, regardless of the duration of the disease to develop the model. Based on clinical data, a feedforward neural network (NN) was implemented - a multilayer perceptron.MATERIALS AND METHODS: Development of the most effective algorithm for predicting MODY in children based on available clinical indicators of 1710 patients with diabetes under the age of 18 years using a multilayer feedforward neural network.RESULTS: The sample consisted of 1710 children under the age of 18 years with T1DM (78%) and MODY (22%) diabetes. For the final configuration of NS the following predictors were selected: gender, age at passport age, age at the diagnosis with DM, HbA1c, BMI SDS, family history of DM, treatment. The performance (quality) assessment of the NN was carried out on a test sample (the area under the ROC (receiver operating characteristics) curve reached 0.97). The positive predictive value of PCPR was achieved at a cut-off value of 0.40 (predicted probability of MODY diabetes 40%). At which the sensitivity was 98%, specificity 93%, PCR with prevalence correction was 78%, and PCR with prevalence correction was 99%, the overall accuracy of the model was 94%.Based on the NN model, a CDSS was developed to determine whether a patient has MODY diabetes, implemented as an application.CONCLUSION: The clinical prediction model MODY developed in this work based on the NN, uses the clinical characteristic available for each patient to determine the probability of the patient having MODY. The use of the developed model in clinical practice will assist in the selection of patients for diagnostic genetic testing for MODY, which will allow for the efficient allocation of healthcare resources, the selection of personalized treatment and patient monitoring.

HNF1A-MODY (maturity-onset diabetes of the young — диабет взрослого типа у молодых лиц) — второй по распространенности тип MODY у детей, характеризующийся аутосомно-доминантным наследованием, прогрессирующей дисфункцией β-клеток с высоким риском хронических микро- и макрососудистых ос- ложнений. В основе заболевания лежат патогенные варианты гена ядерного фактора гепатоцитов 1 альфа (HNF1A), который относится к факторам транскрипции и участвует в дифференцировке и функционирова- нии β-клеток. Пациенты с HNF1A-MODY чувствительны к препаратам сульфонилмочевины (СМ) в низких дозах, по мере прогрессирования заболевания может потребоваться инсулинотерапия. Клинический случай: пациентка Г., 17 лет. Впервые в 12 лет случайно выявлена глюкозурия, кетонов не было. Гликемия натощак 8,5 ммоль/л, гликированный гемоглобин (HbА1c) -7,7%. Клинических симптомов сахарного диабета (СД) не было. Наследственный анамнез по СД отягощен. У матери, 51 год, СД 2 типа без ожирения с 42 л, у тети по ма- теринской линии, 54 года, СД 2 типа с 44 л, получают гликлазид. Через 5 мес после диагностики СД, в 12,5 лет, впервые обследована в ФГБУ «НМИЦ эндокринологии». Колебания гликемии в течение суток 5,2-9,5 ммоль/л, HbА1c 6,3%. По данным ПГТТ (0-60-120 мин) отме- чалась нормогликемия натощак и нарушение толерантности к глюкозе на 120 мин, нормальная секреция инсулина и С-пептида: гликемия 4,4-9,2-9,7 ммоль/л, ИРИ 3,4-24,1-25,6 мкЕ/мл, С-пептид 1,3-5,1-5,0 нг/мл. Специфические островковые антитела отрицательные: к IA2 - 8 Ед/мл (0-10), GADA - 0,40 Ед/мл (0-1), ICA – 0,77 Ед/мл (0-1), IAA – 1,18 Ед/мл. В ходе молекулярно-генетического исследования в 4 экзоне гена HNF1A выявлен патогенный вариант в гетерозиготном положении p.Pro 291ins C frame shift. Пациентке диагности- рован HNF1A-MODY. Тот же вариант выявлен у матери ребенка. Пациентке рекомендована диета с ограни- чением легкоусвояемых углеводов. В 17 лет гипергликемия до 15 ммоль/л, HbА1c 9,1%. Учитывая наличие у пациентки HNF1A-MODY, на- значена терапия глимепиридом 0,5 мг, в дальнейшем с увеличением дозы до 1 мг. На фоне данной терапии отмечалась нормализация показателей гликемии. По данным пробы со стандартным жидким завтраком на чистом фоне (контроль 0-60-120 мин): гликемия 6,1-12,6-9,1 ммоль/л, ИРИ 6,3-21,4-3,3 мкЕ/мл, С-пептид 1,5-4,4-1,7 нг/мл. Проба со стандартным жидким завтраком на фоне приема глимепирида: отмечается уве- личение секреции ИРИ, С-пептида и улучшение показателей гликемии: гликемия 4,7-10,1-7,3 ммоль/л, ИРИ 6,0-32,2-20,2 мкЕ/мл, С-пептид 1,9-6,4-5,3 нг/мл. Через 3 мес наблюдалось снижение уровня HbA1c до 7,1%. ВЫВОДЫ: молекулярно-генетическая диагностика диабета MODY имеет определяющее значение для подбора оптимального лечения пациентов. При выявлении патогенных гетерозиготных вариантов в гене HNF1A рекомендуется назначение препаратов СМ, назначение СМ в минимальной дозе позволяет из- бежать развитие гипогликемий. Описанный случай иллюстрирует высокую эффективность глимепирида у девочки с HNF1A-MODY.

BACKGROUND : Type 1 diabetes mellitus (T1D) is an autoimmune disorder that leads to pancreatic β-cells destruction and progressive decrease of insulin secretion. Specific islet autoantibodies (AAbs) are the main diagnostic marker of T1D. Residual β-cell function, as measured by C-peptide, has repeatedly been demonstrated to be clinically important. AIM: To study the frequency and levels of residual C-peptide secretion and persistence of pancreatic AAbs in children with T1D with different duration and age of manifestation of the disease. MATERIALS AND METHODS : The levels of C-peptide and AAbs to ZnT8 (zinc transporter 8), AAbs to IA-2 (Insulinoma Antigen 2), AAbs to GAD (Glutamate Decarboxylase), IAA (insulin autoantibodies) were measured. Patients were divided into 3 groups depending on the duration of T1D (1st — <1 year, 2nd — from 1 to 5 years, 3rd — >5 years) and age of manifestation (A — prepubertal and B — puberty). RESULTS: The median duration of T1D was 1.8 [0,8;3,9], 76.3% out of 1333 patients were seropositive, 40% had residual levels of C-peptide. With disease duration there were a decrease in AAbs+: 1st group 74%, 2nd group 69%, and 3rd group 48%. In all groups, percentage of patients with positive levels of one or more AAbs was significantly higher in children with T1D manifestation at puberty. GADA and ZnT8A were more common in the first year of the disease. IA-2A were observed with the same frequency in the group of adolescents. IAA were more common in patients at prepubertal age. An undetectable level of C-peptide was observed significantly higher in children with T1D manifestation in prepubertal age (p<0.05): 1А — 13% and 1B — 5%, 2А — 51% and 2B — 14%, 3А — 82% and 3B — 50%, reference range of C-peptide was observed in adolescents (p<0,05): 1А — 6% and 1B — 44%, 2А — 2% and 2b — 25%, 3А — 2% and 3B — 11%. CONCLUSION: AAbs+ is relatively common in children with T1D and about half of them are seropositive in more than 5 years after manifestation. GADA and ZnT8A have high specificity for patients with new-onset T1D. C-peptide secretion depends on the age of the disease manifestation.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Моногенный сахарный диабет (МСД) – это гетерогенная группа нарушений углеводного обмена, в ос- нове которых лежит дефект генов, ассоциированных с секрецией и/или действием инсулина, закладкой и развитием поджелудочной железы. Частота МСД достоверно не известна, по данным различных иссле- дований в детском возрасте его частота составляет 1–6%. Наиболее распространенными формами МСД являются MODY и неонатальный сахарный диабет (НСД). МАТЕРИАЛЫ И МЕТОДЫ: проанализированы данные реестра пациентов с МСД, подтвержденным в ходе молекулярно-генетического исследования (МГИ), за период с 2012 по 2022 годы. Пациенты были обследованы с проведением МГИ в ФГБУ «НМИЦ эндокринологии» Минздрава России. Возраст на момент обследования составил от 0 до 18 лет. РЕЗУЛЬТАТЫ: за период с 2012 по 2022 года обследовано 417 детей с МСД (386 пробандов, 29 сибсов), из которых 382 (91,7%) пациентов с MODY, 17 (4,1%) – с НСД, 9 (2,2%) – с DIDMOAD, 4 (0,9%) – с липоатрофи- ческим сахарным диабетом, 3 (0,7%) – с синдромом инсулинорезистентности типа А, 1 (0,2%) – с синдромом Рабсона-Менденхолла и 1 (0,2%) – с синдромом Альстрема. Наиболее часто у пациентов с фенотипом MODY наблюдался GCK-MODY и HNF1A-MODY, мутации в гене GCK были выявлены у 74% пациентов (n=282), в гене HNF1A выявлены у 12% пациентов (n=45). Более ред- кими причинами MODY были мутации в гене ABCC8, которые выявлены в 1,8% (n=7), в гене HNF4β – в 1,6% (n=6), в гене HNF4A – в 1% (n=4), в гене RFX6 – в 1% (n=4), в гене INSR – в 0,9% (n=3). В единичных случаях были идентифицированы мутации в генах KLF11, NEUROD1, PAX4, PDX1, PTF1A, WFS1 – в 0,5% (n=3) каждая, в генах BLK, CEL, GLIS3, INS – в 0,2% случаев каждая. В 3,5% (n=13) диагностирован MODY с дигенным на- следованием, в 0,4% (n=2) с олигогенным наследованием. Наиболее частой причиной НСД были мутации в гене KCNJ11, которые выявлены у 35,5% пациен- тов (n=6), у 17,8% (n=3) идентифицирована мутация в гене INS, у 11,7% (n=2) – мутация в гене ABCC8, у 1 (n=5,8%) – в гене GATA6. В 11,7% (n=2) НСД был ассоциирован с аномалиями хромосомы 6q24. У одной пациентки НСД диагностирован в составе синдрома Уолкотта-Раллисона, подтвержденного при МГИ (вы- явлена гомозиготная мутация в гене EIF2AK3). У 2 пациентов генетическая причина НСД не установлена. ВЫВОДЫ: под данным реестра МСД в детском возрасте наиболее частой формой МСД является MODY, которая встречается в 91,7% случаях всех форм МСД. Гетерозиготные мутации в гене GCK являются наи- более распространенной причиной MODY у детей (74%). Второй по распространенности подтип у детей – HNF1A- MODY, который выявлен в 12% всех случаях MODY. Частота НСД среди МСД в детском возрасте составила 4,1%, наиболее распространенной причиной НСД являются мутации в гене KCNJ11. СБОРНИК ТЕЗИСОВ III Конференция по лечению и диагностике сахарного диабета «Фундаментальная и клиническая диабетология в 21 веке: от теории к практике»

Insulin resistance type A is a monogenic disorder with insulin action defect, observed in females with acanthosis nigricans (AN), hyperandrogenism, hyperinsulinemia, insulin resistance (IR) without obesity. We present a family case of diabetes mellitus (DM) with IR in two sisters with obesity and positive family history of DM in three generations. Hyperglycemia was identified at the age of 13 in the older sister and at 11 in the younger sister after COVID-19. Type 2 diabetes (DM2) was diagnosed in mother in the same time with children. Maternal grandmother was diagnosed with DM2 in 58 years old. Patients were examined in 6 months after diagnosis hyperglycemia in Endocrinology Research Centre. The older sister had obesity, AN, and striae distensae. Glycosylated hemoglobin (HbA1c) 6.2%. Impaired glucose tolerance (IGT), hyperinsulinemia and IR, hyperandrogenism, non-alcoholic fatty liver disease (NAFLD), arterial hypertension were diagnosed. The younger sister had obesity, striae distensae. HbA1c — 6.0%. Impaired fasting glucose (IFG), IGT, hyperinsulinemia, IR, NAFLD were diagnosed. Antibodies (AAb) to ZnT8A, IA2, GAD absented in both sisters. A genetic test was provided, a heterozygous mutation in the INSR gene p.V167M was identified in both sisters, mother and grandmother. IR type A was identified in a family with the phenotype of DM2 in this case. This case demonstrated that children with carbohydrate metabolism disorders and obesity without Islet cell autoantibodies have to reffered for a genetic testing. Disordered carbohydrate metabolism was diagnosed in the same time after a COVID-19 in three family members who did not previously have disordered carbohydrate metabolism. We suppose that SARS-CoV-2 can be a trigger for the development of carbohydrate metabolism disorders in IR type A.

МУТАЦИИ В ГЕНЕ ГЛЮКОКИНАЗЫ ПРИ СЛУЧАЙНО ВЫЯВЛЕННОЙ ГИПЕРГЛИКЕМИИСечко Е .А