MedElevator
Войти в исследования Muscle & nerve · 2026
Increased Glycogenin-Exposed Residual Glycogen in Lysosomes Is the Early Pathological Finding in Asymptomatic Pompe Disease.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shi Yixin, Zhang Na, Sun Hanhan, Wang Yunyu, Zhao Dandan, Wen Bing, Yan Chuanzhu, Zhao Yuying, Li Duoling
Аннотация
INTRODUCTION/AIMS: Although asymptomatic or pre-symptomatic Pompe disease is increasingly recognized, early skeletal muscle pathology and the role of residual glycogen at this stage remain unclear. Here, we investigated early muscle pathological changes using human samples and an early-stage Gaa -/- mouse model, focusing on residual glycogen accumulation.
METHODS: Clinical, genetic, imaging, and muscle pathological analyses were performed in an asymptomatic Pompe disease patient carrying a novel GAA variant. Skeletal muscle samples from asymptomatic and symptomatic patients, as well as from early-stage and late-stage Gaa -/- mice, were analyzed using histochemistry, immunohistochemistry, immunofluorescence, and Western blotting to assess residual glycogen accumulation and lysosome-associated pathways.
RESULTS: We identified a novel mutation, c.361C > T, in an asymptomatic Pompe disease patient. Despite the lack of symptoms, residual glycogen accumulated in muscle lysosomes. Immunohistochemistry showed positive glycogenin expression, while LAMP1 and LC3 were negative, suggesting early glycogenin detection. Western blot revealed increased glycogenin and STBD1, with mild LAMP1 and LC3 upregulation. In 1-month-old Gaa -/- mice, glycogenin, LAMP1, STBD1, and LC3 were all upregulated. Furthermore, immunofluorescence further showed glycogenin/LAMP1 double-positive muscle fibers in both the patient and mice.
DISCUSSION: Our study shows that key pathological changes in Pompe disease occur during the asymptomatic stage, with early lysosomal accumulation of residual glycogen. This suggests residual glycogen may serve as a biomarker of early disease activity and a potential target for early intervention, informing disease monitoring and the timing of enzyme replacement therapy (ERT). Further studies are needed to validate its clinical utility and explore strategies for early clearance.
METHODS: Clinical, genetic, imaging, and muscle pathological analyses were performed in an asymptomatic Pompe disease patient carrying a novel GAA variant. Skeletal muscle samples from asymptomatic and symptomatic patients, as well as from early-stage and late-stage Gaa -/- mice, were analyzed using histochemistry, immunohistochemistry, immunofluorescence, and Western blotting to assess residual glycogen accumulation and lysosome-associated pathways.
RESULTS: We identified a novel mutation, c.361C > T, in an asymptomatic Pompe disease patient. Despite the lack of symptoms, residual glycogen accumulated in muscle lysosomes. Immunohistochemistry showed positive glycogenin expression, while LAMP1 and LC3 were negative, suggesting early glycogenin detection. Western blot revealed increased glycogenin and STBD1, with mild LAMP1 and LC3 upregulation. In 1-month-old Gaa -/- mice, glycogenin, LAMP1, STBD1, and LC3 were all upregulated. Furthermore, immunofluorescence further showed glycogenin/LAMP1 double-positive muscle fibers in both the patient and mice.
DISCUSSION: Our study shows that key pathological changes in Pompe disease occur during the asymptomatic stage, with early lysosomal accumulation of residual glycogen. This suggests residual glycogen may serve as a biomarker of early disease activity and a potential target for early intervention, informing disease monitoring and the timing of enzyme replacement therapy (ERT). Further studies are needed to validate its clinical utility and explore strategies for early clearance.