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 (p = 0.003)). However, FEV1, FVC and GMFM-88, the median 6MWD and the peak VO2 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 VO2 followed in the decreasing order by 6MWD, FVC and GMFM-88. CONCLUSIONS: The peak VO2 and 6MWD might serve as more sensitive markers to assess clinical deterioration. More studies are needed to clarify the sensitivity of the peak VO2 and 6MWT for quantification of individualized response. This may be important when assessing newer strategies and formulations in IOPD.

Comprehensive cardiopulmonary assessment in α mannosidosis.

INTRODUCTION: α Mannosidosis is an extremely rare, progressive, and complex lysosomal storage disease, characterized by mental retardation, hearing impairment, coarse facial features, skeletal abnormalities, and pulmonary involvement. While bone marrow transplantation has been the only therapeutic option to date, nowadays new treatment options are being explored, which may affect pulmonary and exercise capacity. AIM AND METHODS: To assess cardiopulmonary involvement in patients with α mannosidosis by pulmonary function tests, cardiopulmonary exercise testing, and low irradiation chest computed tomography (CT). RESULTS: Five patients aged 11 to 28 years were followed in our Respiratory-Metabolic Clinic. All five had pulmonary symptoms and received inhaled therapy. Three patients underwent bone marrow transplantation. Parenchymal lung disease was evident in 3/5 chest CT tests. Pulmonary function tests were abnormal in all patients and showed obstructive/restrictive impairment with air trapping. All five patients showed reduced peak oxygen uptake (median 23.1; range 20.4-32.2 mL/minute/kg, median %predicted 62; range %predicted 59-79). CONCLUSIONS: Pulmonary involvement is a known complication in this rare disease. Comprehensive cardiopulmonary evaluation is feasible among these patients and may help in assessing disease progression and response to new treatment modalities.