Pulmonary function and exercise tolerance in glycogenosis type II (GSDII)

Pompe disease is an autosomal recessive myopathy caused by deficiency of the lysosomal enzyme α-glucosidase. Enzyme replacement therapy (ERT) with human recombinant α-glucosidase (rhGAA) is effective in the treatment of infantile forms of GSDII, but experience in late-onset disease is still limited. Aim: To determine ERT long-term effects on pulmonary function and exercise tolerance in late-onset GSDII. Methods: 7 children (mean age at starting ERT 11 years, 4M:3F) receiving bi-weekly infusion of rhGAA for at least 36 months were evaluated performing pulmonary function tests and 6-min walking tests (6MWT), before (T0) and during treatment (T12, T24, T36). Results: Our data describe a predominantly restrictive pattern of lung function at baseline, without a significant improvement after ERT. T0 Median values during ERT FEV1 72.7 (26–110) 85.7 (24–131) FVC 76.7 (27–113) 81.1 (23–119) FEV1/FVC 93 104.4 The 6MWT improved during ERT; analysis of individual performances showed a progressive increase in walking capacity in all the patients. The difference in 6MWT rank distribution at baseline, T12, T24 and T36 was statistically significant (p< 0.05, according to Friedman). Patients T0 T12 T24 T36 1 15* 589 565 590 2 718 782 770 739 3 104 156 156 180 4 643 742 630 649 5 572 548 513 598 6 636 580 562 640 7 680 685 719 720 Median 481 583 559 588 *Patient tracheostomized at T0. Conclusion: Our data highlight as motor and respiratory functions respond differently to ERT: motor function seems to improve due to an increased peripheral muscular endurance, while pulmonary function remains unchanged after starting treatment. Long-term ERT is effective in improving motor function and in stabilizing respiratory function in late-onset GSDII.