Bar-Yoseph Ronen, Tal Galit, Dumin Elena, Hanna Moneera, Mainzer Gur, Zucker-Toledano Merav, Shallufi George, Jahshan Mira, Mandel Hanna, Bentur Lea
Ruth Children's Hospital, Pediatric Pulmonary Institute, Technion Faculty of Medicine, Haifa 3109601, Israel.
Metabolic Unit, Ruth Children's Hospital, Technion Faculty of Medicine, Haifa 3109601, Israel.
J Pers Med. 2021 Oct 28;11(11):1105. doi: 10.3390/jpm11111105.
Enzyme replacement therapy (ERT) with alglucosidase alfa improves the prospect of patients with infantile-onset Pompe disease (IOPD). However, a progressive decline has been reported. Objective quantification of the response to ERT when assessing newer strategies is warranted.
This combined retrospective-prospective study assessed the acute and long-term effects of ERT on exercise in IOPD patients. Evaluation included cardiopulmonary exercise testing (CPET), 6-min walking test (6MWT), spirometry, motor function test (GMFM-88) and enzyme blood levels.
Thirty-four CPETs (17 pre- and 17 two days-post ERT) over variable follow-up periods were performed in four patients. Two days following ERT, blood enzyme levels increased (median, 1.22 and 10.15 μmol/L/h ( = 0.003)). However, FEV1, FVC and GMFM-88, the median 6MWD and the peak VO were unchanged. Long-term evaluations showed stabilization in young patients but progressive deterioration in adolescents. Clinical deterioration was associated with more pronounced deterioration in peak VO followed in the decreasing order by 6MWD, FVC and GMFM-88.
The peak VO and 6MWD might serve as more sensitive markers to assess clinical deterioration. More studies are needed to clarify the sensitivity of the peak VO and 6MWT for quantification of individualized response. This may be important when assessing newer strategies and formulations in IOPD.
用阿糖苷酶α进行酶替代疗法（ERT）可改善婴儿型庞贝病（IOPD）患者的预后。然而，已有报道称病情会逐渐恶化。在评估新策略时，对ERT反应进行客观量化是必要的。
这项回顾性与前瞻性相结合的研究评估了ERT对IOPD患者运动能力的急性和长期影响。评估内容包括心肺运动试验（CPET）、6分钟步行试验（6MWT）、肺量计检查、运动功能测试（GMFM - 88）和血液酶水平。
对4例患者在不同随访期进行了34次CPET（17次ERT前和17次ERT后两天）。ERT后两天，血液酶水平升高（中位数分别为1.22和10.15μmol/L/h，P = 0.003）。然而，第一秒用力呼气容积（FEV1）、用力肺活量（FVC）和GMFM - 88、6MWD中位数以及峰值摄氧量（VO₂peak）均未改变。长期评估显示年轻患者病情稳定，但青少年患者病情逐渐恶化。临床恶化与VO₂peak更明显的恶化相关，其次是6MWD下降、FVC下降和GMFM - 88下降。
VO₂peak和6MWD可能是评估临床恶化更敏感的指标。需要更多研究来阐明VO₂peak和6MWT对量化个体反应的敏感性。这在评估IOPD的新策略和制剂时可能很重要。
