diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM12826diaendo-12826Research ArticleКлинический случайCase reportНеонатальный сахарный диабет в сочетании с врожденным гипотиреозом у пациентки с новой гомозиготной мутацией гена GLIS3Novel GLIS3 mutation in patient with neonatal diabetes mellitus and congenital hypothyroidism (NDH-syndrome)https://orcid.org/0000-0001-7747-6873ТихоновичЮ. В.TikhonovichYu. V.

Тихонович Юлия Викторовна - кандидат медицинских наук; eLibrary SPIN: 6492-6790.

119435 Москва, ул. Большая Пироговская, д. 19, стр. 2

Yulia V. Tikhonovich - MD, PhD; eLibrary SPIN: 6492-6790.

19c2, Bol’shaya Pirogovskaya st., Moscow, 119435

yuliatihonovich@mail.ruhttps://orcid.org/0000-0002-2975-2869ЧерныхЛ. Г.ChernichL. G.

Черных Людмила Геннадьевна - кандидат медицинских наук; eLibrary: SPIN: 3172-2252

Екатеринбург

Liudmila G. Chernich - MD, PhD; eLibrary: SPIN: 3172-2252

Ekaterinburg

lgchern@mail.ruhttps://orcid.org/0000-0003-0082-8724ВеликановИ. Н.VelikanovI. N.

Великанов Игорь Николаевич; eLibrary SPIN: 7541-3301

Екатеринбург

Igor N. Velikanov - MD; eLibrary SPIN: 7541-3301

Ekaterinburg

ivelikanov@mail.ruhttps://orcid.org/0000-0002-8123-9181ПоляковаВ. М.PolyakovaV. M.

Полякова Валентина Михайловна - врач детский эндокринолог; eLibrary SPIN: 1830-3491

Екатеринбург

Valentina M. Polyakova - MD; eLibrary SPIN: 1830-3491

Ekaterinburg

valencia9403@gmail.comhttps://orcid.org/0000-0003-1107-362XВасильевЕ. В.VasilyevE. V.

Васильев Евгений Витальевич - кандидат биологических наук, ведущий научный сотрудник ; eLibrary SPIN: 5767-1569

Москва

Evgeny V. Vasilyev - PhD in Biology, senior research associate; eLibrary SPIN: 5767-1569

Moscow

vas-evg@yandex.ruhttps://orcid.org/0000-0002-0520-9132ПетровВ. М.PetrovV. M.

Петров Василий Михайлович - кандидат химических наук, ведущий научный сотрудник ; eLibrary SPIN: 4358-2147

Москва

Vasily M. Petrov - PhD in Chemistry, senior research associate; eLibrary SPIN: 4358-2147

Moscow

petrov.vasily@gmail.comhttps://orcid.org/0000-0003-0031-1389ШрёдерЕ. В.ShrederE. V.

Шрёдер Екатерина Владимировна - врач детский эндокринолог; eLibrary SPIN: 7997-2501

Москва

Ekaterina V. Shreder - MD; eLibrary SPIN: 7997-2501

Moscow

evshreder@bk.ruhttps://orcid.org/0000-0002-7626-3750ГлаватскихЕ. В.GlavatskichЕ. V.

Главатских Елена Владимировна - врач детский эндокринолог.

Первоуральск

Elena V. Glavatskich - MD

Pervouralsk

glavatskich-ev@mis66.ruhttps://orcid.org/0000-0001-8500-4841ТюльпаковА. Н.TyulpakovA. N.

Тюльпаков Анатолий Николаевич - доктор медицинских наук, профессор; eLibrary SPIN: 8396-1798

Москва

Anatoliy N. Tyulpakov - MD, PhD, Professor; eLibrary SPIN: 8396-1798

Moscow

anatolytiulpakov@gmail.comПервый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский университет); Морозовская ДГКБ ДЗМРоссияSechenov First Moscow State Medical University; Morozov children’s city hospitalRussian FederationОбластная детская клиническая больницаРоссияState Autonomous Healthcare Institution Sverdlovsk Regional children’s clinical hospitalRussian FederationНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CentreRussian FederationМорозовская ДГКБ ДЗМРоссияMorozov children’s city hospitalRussian FederationДетская городская больницаРоссияChildren City HospitalRussian FederationРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова; Медико-генетический научный центр имени академика Н.П. БочковаРоссияPirogov Russian National Research Medical University; Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Russian Academy of SciencesRussian Federation2022230320222518188Copyright © Тихонович Ю.В., Черных Л.Г., Великанов И.Н., Полякова В.М., Васильев Е.В., Петров В.М., Шрёдер Е.В., Главатских Е.В., Тюльпаков А.Н., 20222022Тихонович Ю.В., Черных Л.Г., Великанов И.Н., Полякова В.М., Васильев Е.В., Петров В.М., Шрёдер Е.В., Главатских Е.В., Тюльпаков А.Н.Tikhonovich Y.V., Chernich L.G., Velikanov I.N., Polyakova V.M., Vasilyev E.V., Petrov V.M., Shreder E.V., Glavatskich Е.V., Tyulpakov A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/12826

Мутации в GLI-подобном 3 (GLIS3) гене, кодирующем фактор транскрипции GLIS3, являются причиной редкой синдромальной формы неонатального сахарного диабета (НСД), протекающего с врожденным гипотиреозом (ВГ), врожденной глаукомой, фиброзом печени и другими аномалиями. Данное заболевание в зарубежной литературе получило название NDH-синдром (Neonatal Diabetes and Hypothyroidism syndrome).

В сообщении мы представляем подробное клиническое описание пациентки с данным синдромом. Ребенок был рожден от близкородственного брака, преждевременных родов с низкими весо-ростовыми показателями. Диагноз НСД был установлен на 2-е сутки жизни на основании глюкозурии, стойкого повышения гликемии до 40 ммоль/л. С 3-го дня жизни инициирована инсулинотерапия в микроструйном режиме. На 5-й день жизни по результатам неонатального скрининга верифицирован ВГ: тиреотропный гормон 1242 мМЕ/л, свободный тироксин 2,1 пмоль/л. ­Назначена заместительная терапия левотироксином натрия в стартовой дозе 25 мкг/cут.

Учитывая сочетание НСД, ВГ, задержку внутриутробного развития, был заподозрен NDH-cиндром. В 2 мес жизни ребенку было проведено молекулярно-генетическое исследование.

В 5 экзоне гена GLIS3 (NM_001042413.2) выявлен гомо(геми)зиготный вариант c.1836delT, p.Ser612ArgfsTer33 — ­делеция 1 нуклеотида в 1836 положении, приводящая к сдвигу рамки считывания и преждевременной терминации трансляции.

В настоящее время период наблюдения за пациенткой составил 3 года. Сохраняется задержка роста, психомоторного и речевого развития. ВГ и НСД субкомпенсированы на фоне заместительной терапии. Другие компоненты синдрома не выявлены.

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.

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The authors declare that there are no conflicts of interest present.