neurojourНеврологический журнал имени Л.О. БадалянаL.O. Badalyan Neurological Journal2686-89972712-794XФГАУ «НМИЦ здоровья детей» Минздрава России10.46563/2686-8997-2022-3-3-122-126neurojour-72Research ArticleКЛИНИЧЕСКИЕ СЛУЧАИCLINICAL CASESКлинический случай POL3A-ассоциированной гипомиелинизирующей лейкодистрофии с поражением спинного мозга с дебютом в раннем детском возрастеA clinical case of POL3A-associated hypomyelinating leukodystrophy with spinal cord lesion with a debut in early childhoodhttps://orcid.org/0000-0002-9697-500XПоповичСофия ГеоргиевнаPopovichSofia G.

ладший научный сотрудник лаборатории нервных болезней ФГАУ «НМИЦ здоровья детей» Минздрава России.

e-mail: popovich.sg@nczd.ru

MD, junior researcher of the Laboratory of nervous diseases of the National Medical Research Center for Children’s Health of the Ministry of Health of the Russian Federation, Moscow, 119991, Russian Federation.

e-mail: popovich.sg@nczd.ru

popovich.sg@nczd.ruhttps://orcid.org/0000-0002-9562-3774КузенковаЛ. М.KuzenkovaLyudmila M.noemail@neicon.ruhttps://orcid.org/0000-0002-6316-9992КондаковаО. Б.KondakovaOlga B.noemail@neicon.ruФирумянцА. И.FirumyantsAlexey I.noemail@neicon.ruПодклетноваТ. В.PodkletnovaTatyana V.noemail@neicon.ruhttps://orcid.org/0000-0002-8381-8793УвакинаЕ. В.UvakinaEugeniya V.noemail@neicon.ruФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава РоссииNational Medical Research Center for Children’s Health” of the Ministry of Health of the Russian Federation20221810202233122126Copyright © Попович С.Г., Кузенкова Л.М., Кондакова О.Б., Фирумянц А.И., Подклетнова Т.В., Увакина Е.В., 20222022Попович С.Г., Кузенкова Л.М., Кондакова О.Б., Фирумянц А.И., Подклетнова Т.В., Увакина Е.В.Popovich S.G., Kuzenkova L.M., Kondakova O.B., Firumyants A.I., Podkletnova T.V., Uvakina E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.neuro-journal.ru/jour/article/view/72

Лейкодистрофии — это группа наследственных прогрессирующих заболеваний центральной нервной системы, характеризующихся избирательным поражением белого вещества со специфическим вовлечением глиальных клеток. Выделяют гипомиелинизирующие (отсутствие отложения миелина), демиелинизирующие (потеря ранее отложенного миелина), дисмиелинизирующие (отложение структурно или биохимически аномального миелина) и миелинолитические лейкодистрофии (вакуолизация миелина).

Гипомиелинизирующие лейкодистрофии (ГЛ), как и большинство лейкодистрофий, дебютируют в детском или подростковом возрасте и характеризуются прогрессирующим течением заболевания. ГЛ возникает вследствие нарушения синтеза белков, ответственных за развитие, структуру и целостность миелиновой оболочки, а также участвующих в процессах транскрипции и трансляции. В последней группе основная роль отведена ГЛ, ассоциированным с биаллельными мутациями в генах транскрипционного комплекса РНК-полимеразы III — POLR3: POLR3A, POLR3B, POLR1C и POLR3K. Диагноз можно подтвердить с помощью магнитно-резонансной томографии головного мозга.

POLR3А-ассоциированные ГЛ проявляются гипомиелинизацией, гиподонтией и гипогонадотропным гипогонадизмом. К магнитно-резонансным признакам POLR3-ассоциированной ГЛ относят диффузную гипомиелинизацию с относительным сохранением зубчатых ядер, переднебоковых ядер таламуса, бледных шаров, пирамидных путей на уровне задней части внутренних капсул и лучистого венца. В ряде случаев отмечены также истончение мозолистого тела и атрофия мозжечка.

В статье представлен клинический случай пациентки с POL3A-ассоциированной ГЛ с поражением спинного мозга с дебютом в раннем детском возрасте.

Участие авторов

Участие авторов:Попович С.Г. — концепция, написание текста, редактирование текста;Увакина Е.В. — концепция, написание текста, редактирование текста;Подклетнова Т.В. — концепция, написание текста, редактирование текста;Кондакова О.Б. — концепция, написание текста, редактирование текста;Фирумянц А.И. — концепция, редактирование текста;Кузенкова Л.М. — концепция; редактирование текста;Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.

Финансирование

Финансирование. Исследование не имело спонсорской поддержки.

Конфликт интересов

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Поступила 19

Поступила 19.08.2022 Принята к печати 05.09.2022Опубликована 30.09.2022

Leukodystrophies are a group of hereditary progressive diseases of the central nervous system characterized by selective lesions in white matter with specific involvement of glial cells.  There are hypomyelinating (absence of myelin deposition), demyelinating (loss of previously deposited myelin), dysmyelinating (deposition of structurally or biochemically abnormal myelin), and myelinolytic leukodystrophies (myelin vacuolization).

Hypomyelinating leukodystrophies (HL), like most leukodystrophies, debut in childhood or adolescence and are characterized by a progressive course of the disease.  HL occurs as a result of impaired synthesis of proteins responsible for the development, structure, and integrity of the myelin sheath, involved in the processes of transcription and translation.  In the latter group, the main role is assigned to HL associated with biallelic mutations in the genes of the RNA polymerase III transcription complex, POLR3: POLR3A, POLR3B, POLR1C and POLR3K. The diagnosis can be confirmed by magnetic resonance imaging of the brain.

POLR3A-associated HL is manifested by hypomyelination, hypodontia, and hypogonadotropic hypogonadism.  The magnetic resonance features of POLR3-associated HL include diffuse hypomyelination with relative preservation of the dentate nuclei, anterolateral nuclei of the thalamus, globus pallidus, pyramidal tracts at the level of the posterior part of the internal capsules, and the corona radiata.  In some cases, thinning of the corpus callosum and atrophy of the cerebellum were also noted.

The article presents a clinical case of a patient with POL3A-associated HL with spinal cord injury with the debut in early childhood.

Contribution

Contribution: Popovich S.G. — concept, text writing, text editing;Uvakina E.V. — concept, text writing, text editing;Podkletnova T.V. — concept, text writing, text editing;Kondakova O.B. — concept, text writing, text editing;Firumyants A.I. — concept, text editing;Kuzenkova L.M. — concept,  text editing.All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements

Acknowledgements. The study had no sponsorship.

Conflict of interest

Conflict of interest. The authors declare no conflict of interest.

Received

Received: August 19, 2022Accepted: September 09, 2022Published: September 30, 2022

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