Ravaglia Sabrina, de Giuseppe Rachele, Carlucci Annalisa, Jehne Susan, Crescimanno Grazia, Ahmad Lara, Paoletti Matteo, Clemente Gabriele, Pichiecchio Anna, Bazzano Rosella, Cirio Serena, Valente Enza Maria, Danesino Cesare, De Filippi Paola, Tartara Alice, Cena Hellas
IRCCS Mondino Foundation, Pavia, Italy.
Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy.
Front Cell Dev Biol. 2022 Feb 18;10:793566. doi: 10.3389/fcell.2022.793566. eCollection 2022.
Late-onset Pompe disease (LOPD) is an autosomal-recessive metabolic myopathy caused by deficiency of the lysosomal enzyme Acid Alpha-Glucosidase (GAA), leading to glycogen accumulation in proximal and axial muscles, and in the diaphragm. Enzyme Replacement Therapy (ERT) with recombinant GAA became available in 2006. Since then, several outcome measures have been investigated for the adequate follow-up of disease progression and treatment response, usually focusing on respiratory and motor function. Prognostic factors predicting outcome have not been identified till now. In this single Centre, prospective study, we evaluate the response to enzyme replacement therapy in 15 patients (7 males) with LOPD in different stages of disease, aged 49.4 ± 16.1, followed-up for 15 years. Treatment response was measured by the 6-min walking test, vital capacity in supine and upright position, respiratory muscle strength, muscle MRI, manual muscle testing. We investigated the usefulness of Body Impedance Vectorial Analysis for serial body composition assessment. Although most patients with LOPD benefit from long-term treatment, some secondary decline may occur after the first 3-5 years. Some nutritional (lower body mass index, higher fat free mass, higher phase angle) and disease parameters (higher creatinine and shorter disease duration at the beginning of treatment) seem to predict a better motor outcome. Lower Phase Angle, possibly reflecting loss of integrity of skeletal muscle membranes and thus treatment mis-targeting, seems to correlate with worse treatment response on long-term follow-up. Body Impedance Vectorial Analysis is a fast, easily performed and cheap tool that may be able to predict long-term treatment response in patients with LOPD. Low Phase angle may serve as a marker of muscle quality and may be used to predict the response to a muscle-targeted intervention such as ERT, thus improving the identification of patients needing a closer follow-up due to higher fragility and risk of deterioration.
晚发型庞贝病（LOPD）是一种常染色体隐性代谢性肌病，由溶酶体酶酸性α-葡萄糖苷酶（GAA）缺乏引起，导致糖原在近端和躯干肌肉以及膈肌中蓄积。2006年开始有重组GAA的酶替代疗法（ERT）。从那时起，人们研究了几种结局指标，用于对疾病进展和治疗反应进行充分的随访，通常侧重于呼吸和运动功能。到目前为止，尚未确定预测结局的预后因素。在这项单中心前瞻性研究中，我们评估了15例（7例男性）处于疾病不同阶段的LOPD患者对酶替代疗法的反应，这些患者年龄为49.4±16.1岁，随访了15年。通过6分钟步行试验、仰卧位和直立位肺活量、呼吸肌力量、肌肉磁共振成像、徒手肌力测试来衡量治疗反应。我们研究了人体阻抗矢量分析用于连续身体成分评估的效用。尽管大多数LOPD患者从长期治疗中获益，但在最初3至5年后可能会出现一些继发性下降。一些营养指标（较低的体重指数、较高的去脂体重、较高的相位角）和疾病参数（治疗开始时较高的肌酐水平和较短的病程）似乎预示着更好的运动结局。较低的相位角可能反映骨骼肌膜完整性的丧失，从而提示治疗靶向错误，在长期随访中似乎与较差的治疗反应相关。人体阻抗矢量分析是一种快速、易于操作且廉价的工具，可能能够预测LOPD患者的长期治疗反应。低相位角可作为肌肉质量的标志物，可用于预测对诸如ERT等肌肉靶向干预的反应，从而有助于识别由于更高的脆弱性和恶化风险而需要更密切随访的患者。
