Individualized Assessment of Exercise Capacity in Response to Acute and Long-Term Enzyme Replacement Therapy in Pediatric Pompe Disease.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.