Background: Currently more than 50 mutations of the INS gene are known to affect the various stages of insulin biosynthesis in the beta cells of the pancreas. However only individual cases of diabetes mellitus (DM) associated with heterozygous mutations in the coding region of the INS gene were reported in Russian Federation. We report a group of patients with a clinical manifestation of DM caused by mutations in both coding and non-coding regions of the INS gene. The patients with a mutation in the intron of the INS gene are reported for the first time in Russian FederationMaterials and methods: 60 patients with an isolated course of neonatal DM (NDM), 52 patients with a manifestation of DM at the age of 7–12 months and the absence of the main autoimmune markers of type 1 DM, 650 patients with the MODY phenotype were included in the study. NGS technology was used for molecular genetic research. Author’s panel of primers (Custom DNA Panel) was used for multiplex PCR and sequencing using Ion Ampliseq™ technology. The author’s panel “Diabetes Mellitus” included 28 genes (13 candidate genes of MODY and other genes associated with DM).Results: 13 heterozygous mutations were identified in 16 probands and 9 relatives. The majority of mutations were detected in patients with PNDM (18.75%) and in patients with an onset of DM at the age of 7–12 months (9.6%). Mutations in the INS gene were detected in 2 patients (0.3%) in the group with the MODY phenotype. Mutations in the INS gene were not detected in patients with transient NDM (TNDM). Analysis of clinical data in patients with PND and onset of diabetes at the age of 7–12 months did not show significant differences in the course of the disease. The clinical characteristics of the cases of MODY10 and diabetes caused by a mutation in the intron of the INS gene are reported in details.Conclusion: The role of INS gene mutations in NDM, MODY, and DM with an onset at the age of 7–12 months was analyzed in a large group of patients. The clinical characteristics of DM due to a mutation in the intron of the INS gene are reported for the first time in the Russian Federation.
Mutations in the GLIS3 gene encoding the GLIS3 transcription factor are cause of a rare syndromic form of neonatal diabetes mellitus (NDM) with congenital hypothyroidism. Additional features include congenital glaucoma, hepatic fibrosis, polycystic kidneys, developmental delay and other anomalies. This disease in foreign literature is called NDH-syndrome (Neonatal diabetes and Hypothyroidism syndrome).We present the description of a patient with this syndrome with novel homozygous GLIS3 mutation.Our patient is a female, who was born with a weight of 1680 gr, length of 44 cm to consanguineous parents. She developed diabetes on 2 day after birth, requiring continuous intravenous insulin. On day 5 of life hypothyroidism was identified. Thyroid anatomy was normal on ultrasound scan. NDH syndrome was suspected.Genetic analysis revealed a novel homozygous mutation c.1836delT, p.Ser612ArgfsTer33 in exon 5 in GLIS3 gene.To date, the patient is followed up for 4 years in total. Currently, growth retardation, psychomotor and speech development persist. Carbohydrate metabolism and thyroid profile has been subcompensated against the background of replacement therapy. No other components of the syndrome have been identified.In this report, we have demonstrated the features of the neonatal diabetes mellitus in a patient with a defect in the GLIS3 gene. Early genetic verification of the diagnosis contributes to the timely starting of personalized therapy, can improve the quality of life of such patients, and, given the nature of inheritance, is necessary for medical genetic counseling of the family.
Витамин D и его метаболиты играют ключевую роль в поддержании гомеостаза кальция в организме. Нарушение инактивации активного метаболита витамина D 3-1,25-дигидроксивитамина D 3-в результате мутаций в гене CYP24A1 приводит к развитию клинически значимой гиперкальциемии, гиперкальциурии, вторичному гипопаратиреозу, формированию нефрокальциноза и мочекаменной болезни (МКБ). Это состояние получило название «идиопатическая инфантильная гиперкальциемия». Тяжесть заболевания варьирует от бессимптомной гиперкальциемии и гиперкальциурии до тяжелых случаев с летальным исходом в раннем возрасте. Ведение пациентов включает назначение диеты с низким содержанием кальция в пище, регидратации, диуретиков, ограничение инсоляции, а также исключение препаратов, содержащих витамин D. В тяжелых случаях решается вопрос о назначении глюкокортикоидов, кетоконазола, бифосфонатов, проведении гемодиализа. Ранняя диагностика заболевания позволяет разработать индивидуальный план ведения таких пациентов, предотвратить формирование почечной патологии, проводить медико-генетическое консультирование семьи. В статье приведено описание первой в РФ группы пациентов (2 взрослых, 3 детей) с генетически подтвержденным дефектом 24-гидроксилазы; изложены основные клинико-лабораторные характеристики, принципы диагностики и основы ведения пациентов с данной патологией.
For the first time in the domestic literature, the article presents a clinical observation of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 in the 6-year-old patient with manifestation of type 1 diabetes mellitus (T1DM) in the form of diabetic ketoacidosis. Anamnestic, clinical and laboratory data are presented on the basis of which two life-threatening diseases was diagnosed, as well as tactics of therapy, which made it possible to achieve a positive result. This clinical observation is compared with observations of foreign colleagues. Possible pathogenetic mechanisms of MIS-C and T1DM comorbidity are discussed.
The article presents a clinical case of insulin-dependent diabetes mellitus in combination with severe autoimmune enteropathy in a patient at an early age with a new compound heterozygous mutation in the LRBA gene. Anamnestic, clinical and laboratory data, as well as the results of exome sequencing, on the basis of which the diagnosis was established, are given.
Often transfusions red blood cells in patients with hereditary anemias lead to iron overload, that can cause endocrine complications, such as growth retardation, hypothyroidism, hypogonadism, and disorders of carbohydrate metabolism.Clinical case 1. A boy with transfusion-dependent (TD) Diamond-Blackfan anemia at 16.3 years presented with impaired fasting glucose, growth hormone (GH) deficiency, hypogonadotropic hypogonadism; GH therapy was initiated. At the age of 16.8 years old secondary hypothyroidism, secondary hypocorticism and diabetes mellitus were diagnosed. At 17.2 years continuous glucose monitoring (CGM) detected glucose elevations up to 11.7 mmol/l. Therapy with GH and testosterone ethers was continued; levothyroxine and cortef were stopped by patient. At 17.9 years height was 163 cm; no data supporting hypothyroidism nor hypocorticism; glycaemia within goal range.Clinical case 2. A girl with TD beta-thalassemia major at the age of 11.5 years presented with GH deficiency; GH therapy has been conducted from 12.8 to 15.3 years of age. At 13.8 years retardation of pubertal development was diagnosed. At 15.0 hyperglycemia 7.2 mmol/l was detected; normal results of oral glucose tolerance test (OGTT) were observed; glycemia elevations were up to 9.5 mmol/l according to CGM data. At 16.0 height was 152 cm; because of pubertal development arrest hormone replacement therapy was prescribed.CONCLUSION. Growth, pubertal and carbohydrate metabolism disorders were diagnosed in patients with TD hereditary anemias, that confirms the necessity of regularly endocrine investigation. To detect impairment of carbohydrate metabolism investigation of fasting blood glucose, OGTT, and CGM is recommended; glycated hemoglobin measurement is not considered reasonable.
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