Новая мутация в гене TYMP: клинико-морфологическая характеристика пациента с синдромом MNGIE

Синдром митохондриальной нейрогастроинтестинальной энцефаломиопатии – редкое (1–9:1000000, Orphanet, 2021) генетическое мультисистемное заболевание, обусловленное мутациями в ядерном гене TYMP, кодирующем фермент тимидинфосфорилазу.
Представлены данные 13‑летнего наблюдения пациентки Д., 40 лет, с синдромом митохондриальной нейрогастроинтестинальной энцефаломиопатии, связанным с ранее не описанной миссенс‑заменой c.1301G>T (p.Gly434Val) в гене TYMP. Диагноз синдрома митохондриальной нейрогастроинтестинальной энцефаломиопатии был поставлен на основании клинических проявлений (дисфункция желудочно‑кишечного тракта, кахексия, блефароптоз, офтальмопарез, периферическая полинейропатия и лейкоэнцефалопатия), результатов электронейромиографии (демиелинизация с вторичной аксонопатией), а также повышения уровня дигидротимина в сыворотке крови при нормальных уровнях тимидина и дезоксиуридина. Патогистологическое исследование выявило атрофию продольного (наружного) мышечного слоя тонкой и толстой кишок и значимое уменьшение количества CD117+‑клеток (телоцитов), поражение скелетных мышц смешанного характера с преобладанием миогенного паттерна, а также деструкцию миелиновых оболочек периферических нервов. Исследование S100‑положительных вегетативных образований кишечной стенки не выявило патологических изменений. При гистохимическом исследовании не были обнаружены «рваные красные волокна», характерные для митохондриопатий. Трансмиссионная электронная микроскопия продемонстрировала наличие полиморфизма митохондрий кардиомиоцитов и мегаломитохондрий лейомиоцитов кишечника.

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