Porcino M, Musumeci O, Usbergo C, Pugliese A, Arena I G, Rodolico C, Schoser B, Toscano A
UOC of Clinical Neurology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
ERN-NMD Center for Neuromuscular Disorders of Messina - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
Neuromuscul Disord. 2025 Feb;47:105277. doi: 10.1016/j.nmd.2025.105277. Epub 2025 Jan 14.
Late-onset Pompe disease (LOPD) includes patients from 1 year of age to adulthood. The vast heterogeneity in clinical manifestations and disease progression is not fully explained; however, a short disease duration and a young age seem to be good predictors of a better response to treatment. For this purpose, we investigated and followed up a cohort of 13 juvenile patients with LOPD from the clinical and therapeutic point of view, mainly pointing out the transition from presymptomatic to symptomatic status. We retrospectively collected clinical, morphological, biochemical and molecular data from 13 juvenile LOPD patients. Motor and respiratory functional data, obtained during annual follow-up visits, were analyzed. The data included serial evaluations of the Medical Research Council (MRC) scale, the 6-Minute Walking Test (6MWT), the Gait, Stairs, Gower, and Chair (GSGC) score, and seated and supine Forced Vital Capacity (FVC). Muscle Magnetic Resonance Imaging (MRI) was also included, although it was not performed in all cases. Currently, patients mean age is 18 years. All patients but one were diagnosed because of an isolated hyperCKemia: the mean age at diagnosis was 6.8 years (range 1-18). The onset of symptoms occurred from 6 months to 12 years after the diagnosis. The mean clinical follow-up duration was 9 years (range 2-18). From the genetic point of view, the most shared mutation was c.32-13T>G, found in twelve patients as compound heterozygosis. Seven patients underwent muscle biopsy, which showed vacuolar myopathy with glycogen accumulation in four of them with unspecific changes in the other three cases. Five patients developed proximal muscle weakness during the follow-up with a mild waddling gait and a positive Gowers manoeuver. Muscle MRI revealed mild hypotrophy of the thighs at the development of symptoms in four out of five cases. Four patients started alglucosidase alfa, and one avalglucosidase alfa. These five patients on Enzyme Replacement Therapy (ERT) showed motor and respiratory stability in the following years. Timely identification of emerging clinical manifestations in presymptomatic LOPD patients, as a result of careful follow-up, is essential to start prompt treatment to modify the disease natural course.
晚发型庞贝病（LOPD）患者年龄范围从1岁至成年。临床表现和疾病进展存在巨大异质性，目前尚未完全明确其原因；然而，病程较短且发病年龄较轻似乎是对治疗反应较好的良好预测指标。为此，我们从临床和治疗角度对一组13例青少年LOPD患者进行了调查和随访，主要关注从无症状状态到有症状状态的转变。我们回顾性收集了13例青少年LOPD患者的临床、形态学、生化和分子数据。对年度随访期间获得的运动和呼吸功能数据进行了分析。数据包括医学研究委员会（MRC）量表、6分钟步行试验（6MWT）、步态、楼梯、高尔氏征和椅子（GSGC）评分以及坐位和仰卧位用力肺活量（FVC）的系列评估。肌肉磁共振成像（MRI）也纳入其中，不过并非所有病例都进行了该项检查。目前，患者的平均年龄为18岁。除1例患者外，所有患者均因孤立性高肌酸激酶血症而确诊：确诊时的平均年龄为6.8岁（范围1 - 18岁）。症状出现于确诊后6个月至12年。平均临床随访时长为9年（范围2 - 18年）。从遗传学角度来看，最常见的突变是c.32 - 13T>G，12例患者为复合杂合子。7例患者接受了肌肉活检，其中4例显示有空泡性肌病伴糖原蓄积，另外3例有非特异性改变。5例患者在随访期间出现近端肌无力，伴有轻度蹒跚步态和高尔氏征阳性。5例中有4例在症状出现时肌肉MRI显示大腿轻度萎缩。4例患者开始使用阿糖苷酶α，1例使用阿伐糖苷酶α。这5例接受酶替代疗法（ERT）的患者在随后几年中运动和呼吸功能保持稳定。通过仔细随访及时识别无症状LOPD患者出现的临床表现，对于尽早开始治疗以改变疾病自然病程至关重要。
