vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v20i1.2239vsp-2534Research ArticleКЛИНИЧЕСКОЕ НАБЛЮДЕНИЕCLINICAL OBSERVATIONSМитохондриальная энцефаломиопатия, обусловленная недостаточностью пируватдегидрогеназного комплекса: восемь клинических случаевMitochondrial Encephalomyopathy Associated with Pyruvate Dehydrogenase Complex Deficiency: Eight Clinical Caseshttps://orcid.org/0000-0001-7146-7220НиколаеваЕ. А.NikolaevaEkaterina A.

Москва.

Moscow.

https://orcid.org/0000-0002-4147-2309ВолгинаС. Я.VolginaSvetlana Ya.

Волгина Светлана Яковлевна - доктор медицинских наук, профессор кафедры госпитальной педиатрии Казанского ГМУ.420012, Казань, ул. Бутлерова, д. 49.

Kazan.

volgina_svetlana@mail.ruhttps://orcid.org/0000-0001-6667-7725ХалиуллинаЧ. Д.KhaliullinaChulpan D.

420012, Казань, ул. Бутлерова, д. 49.

Kazan.

БоченковС. В.BochenkovSergey V.

Москва.

Moscow.

ДанцеваМ. А.DancevaMaria A.

Москва.

Moscow.

Российский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияPirogov Russian National Research Medical UniversityRussian FederationКазанский государственный медицинский университетРоссияKazan State Medical UniversityRussian Federation2021290120212018186Copyright © Николаева Е.А., Волгина С.Я., Халиуллина Ч.Д., Боченков С.В., Данцева М.А., 20212021Николаева Е.А., Волгина С.Я., Халиуллина Ч.Д., Боченков С.В., Данцева М.А.Nikolaeva E.A., Volgina S.Y., Khaliullina C.D., Bochenkov S.V., Danceva M.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/2534

Обоснование. Дефекты пируватдегидрогеназного комплекса (ПДК), участвующего в интеграции продуктов гликолиза в энергетический метаболизм клеток, являются одной из причин развития митохондриальной патологии. Диагностика заболевания может вызывать значительные трудности, в т. ч. и по причине отсутствия описания российских больных с митохондриальной энцефаломиопатией, вызванной дефицитом ПДК. Описание клинических случаев. Проведен анализ полиморфизма клинических проявлений прогрессирующей митохондриальной энцефаломиопатии, обусловленной патогенными вариантами ядерного Х-сцепленного гена PDHA1 (кодирует альфа-субъединицу пируватдегидрогеназы), у 8 мальчиков в возрасте от 1 до 8 лет. Во всех случаях имело место неблагоприятное течение перинатального периода. К моменту обследования в стационаре основу симптомокомплекса составляли задержка психомоторного развития, атаксия, миопатические проявления. Дистонические атаки наблюдали у 2 сибсов. У всех пациентов при магнитно-резонансной томографии головного мозга были обнаружены изменения: в базальных ядрах — у 6 детей, вентрикуломегалия — у 2. У всех детей определялась гиперлактатацидемия. По данным клинического обследования у 4 пациентов выявлялась более тяжелая степень поражения нервной системы, у 4 детей — средней степени тяжести. Миссенс-мутации гена PDHA1 обнаружены у 6 детей, инсерции c дупликациями, включающими 6 и 16 пар оснований, — у 2. В результате комплексного лечения у детей отмечена умеренная положительная динамика: стабилизация состояния, отсутствие метаболических кризов, снижение частоты эпизодов дистонии. Заключение. Описан клинический полиморфизм митохондриальной энцефаломиопатии, обусловленной дефицитом ПДК. Показаны различия в проявлениях тяжелой и среднетяжелой формы болезни. Представленное описание может быть полезным для медико-генетического консультирования и оказания медико-генетической помощи семье.

Background. Defects in pyruvate dehydrogenase complex (PDC), involved in the glycolysis products integration into the cells' energy metabolism, are one of the reasons of mitochondrial pathology development. The diagnosis of this condition can be pretty complicated also due to the lack of description of such patients with encephalomyopathy associated with PDC deficiency in Russian population. Clinical Cases Description. We have performed the analysis of clinical manifestations polymorphism of progressive mitochondrial encephalomyopathy caused by pathogenic variants in nuclear X linked gene, PDHA1 (encodes alpha subunit of pyruvate dehydrogenase), in 8 boys aged from 1 to 8 years. The adverse perinatal period was mentioned in all cases. The major features of symptom complex by the time of hospital examination were psychomotor retardation, ataxy, myopathic manifestations. Dystonic attacks were observed in 2 sibs. All patients had changes on brain magnetic resonance imaging: in basal ganglia in 6 children and ventriculomegaly in 2 children. All children had lactic acidosis. Clinical examination has shown that 4 patients had severe damage of nervous system, other 4 patients had moderate damage. Missense mutations in the PDHA1 gene were revealed in 6 children, insertions and duplications including 6 and 16 base pairs — in 2 children. The moderate positive dynamics was noticed as a result of complex treatment of children: stabilization of the overall condition, no metabolic crises, decrease in frequency of dystonic attacks. Conclusion. The clinical polymorphism of mitochondrial encephalomyopathy associated with PDC deficiency is described. The differences in manifestations of severe and moderate forms of disease are shown. The presented description may be useful for medico-genetic counseling and providing medico-genetic care for families.

детимитохондриальная энцефаломиопатиядефицит пируватдегидрогеназыген PDHA1диагностикафакторы рискалечениеchildrenmitochondrial encephalomyopathypyruvate dehydrogenase deficiencyPDHA1 genediagnosticsrisk factorstreatmentНе указан.Not specified.ReferencesDiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med. 2003;26(348):2656-2668. doi: 10.1056/NEJMra022567DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med. 2003;26(348):2656-2668. doi: 10.1056/NEJMra022567Haas RH, Parikh S, Falk MJ, et al. Mitochondrial disease: a practical approach for primary care physicians. Pediatrics. 2007; 120(6):1326-1333. doi: 10.1542/peds.2007-0391Haas RH, Parikh S, Falk MJ, et al. Mitochondrial disease: a practical approach for primary care physicians. Pediatrics. 2007; 120(6):1326-1333. doi: 10.1542/peds.2007-0391Poole OV, Hanna MG, Pitceathly RD. Mitochondrial disorders: disease mechanisms and therapeutic approaches. 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The authors declare that there are no conflicts of interest present.