CLINICAL SCIENCES Improved Exercise Tolerance after Enzyme Replacement Therapy in Pompe Disease MAURO MARZORATl', SIMONE PORCELLi'-, BARBARA REGGIORI^ LUCIA MORANDl\ and BRUNO GRASSI^ 'Institute of Bioimaging and Molecular Physiology, CNR, Segrate, Milan, ITALY; ^Università Telemática San Raffaele, Rome, ITALY; ^Movement Disorders Unit, Fondazione IRCCS Istitiito Neurologico "Carlo Besta, " Milan. ITALY; ''Netiramtisctilar Disea.ses and Neiiroimmtinology Unit, Fondazione IRCCS Istituto Ncuroiogico "Carlo Besta, " Milan, ITAL Y; and ' Department of Medical and Bioiogical Sciences, University ofUdine, Udine, ITALY ABSTRACT MARZORATl. M.. S. PORCELLI. B. REGGIORI, L. MORANDI. and B. GRASSI. Improved Exercise Tolerance afier Enzyme Replacement Therapy in Pompe Disease. Med. Sei. Sports Exere.. Vol. 44, No. 5. pp. 11\~115. 2012. Purpose: Enzyme replacement therapy (ERT) has recently became available tor Pompe disease. Data on the effects of ERT on physiological variables related to exercise tolerance have never been published. Methods: Pulmonary gas exchange, cardiac output (by impedance cardiography). and vastus Iateralis muscle O, extraction (by near-infrared spectroscopy) were determined during cycle ergometer exercise in a 50-yr-old patient before and after 1,12. and 24 months of ERT. Results: At the same constant-workload suhmaximal exercise. RPE. R, pulmonary ventilation, and HR were lower during ERT versus before, suggesting an increased exercise tolerance. Peak oxygen uptake (VOipeak) increased by -35% from before (0.64 Lmin" ' or 11.4 mL-kg"'min"') to 1 month (0.88 Lmin ' or 15.7 mL-kg"'-min') of treatment and did not significantly change thereafter. Also, peak cardiac output significantly increased during ERT, whereas peak skeletal muscle fractional O2 extraction was unchanged compared with before. Conclusions: Improvements of peak exercise capacity and exercise tolerance at submaximal workloads were observed in a patient with Pompe disease after 1 month of ERT. with no further changes during the ensuing treatment period (up to 24 months). Key Words: GLYCOGEN STORAGE DISEASE TYPE II, CYCLE ERGOMETER EXERCISE, CARDIAC OUTPUT, 0 , UPTAKE, NEAR-INFRARED SPECTROSCOPY P ompe disease, also known as glycogenosis type II or acid maltase deficiency, is an inherited myopa- thy caused by the deficiency of lysosomal acid tt-glucosidase (GAA) or acid maltase. The enzyme cata- lyzes the hydrolysis of a-1,4 and a-1,6 links of glycogen and its deficiency leads to intralysosomal accumulation of glycogen. The disease presents as a continuum of clinical phcnotypc, varying according to age at onset, organ in- volvement, and severity of progression. The severe infantile disease is characterized by generalized muscle weakness, hypertrophie cardiomyopathy, and an invariably fatal out- come by 1 yr of age. Patients with late-onset Pompe disease present with progressive muscle weakness that can also af- Address for correspondence: Mauro Marzorati. M.D.. Ph.D., Istituto di Bioimmagini e Fisiologia Molecolare, Consiglio Nazionale delle Ricerehe, L.I.T.A., Via Fratelli Cervi 93, 1-20090 Segrate, Milan, Italy; E-mail: mauro.marzorati@ibfni.cnr.it. Submitted for publication May 2011. Accepted for publication October 2011. 0195-9131/12/4405-0771/0 MEDICINE & SCIENCE IN SPORTS & EXERCISE» Copyright © 2012 by the American College of Sports Medicine DOI: 10.1249/MSS.0b0l3e31823e6579 feet pulmonary function. A considerable number of patients become wheelchair dependent and may require assisted ven- tilation later in life (8). An inverse correlation is usually observed between the amount of residual GAA activity and disease severity, and in general, the symptoms do not emerge until the GAA activity remains above 30% of average nor- mal activity (23). According to Nascimbene et al. (12), patients with Pompe disease would have a predominant ex- pression of inactive forms of GAA protein and severely re- duced or absent levels of mature forms, and disease severity would be primarily detennined by the amount of functional protein. Until recently, no effective therapy for Pompe disease was available, even if positive effects have been reported with a combination of high-protein and low-carbohydrate nutri- tion and exercise (18). Enzyme replacement therapy (ERT) with recombinant human a-glucosidase became available in 2000 (20), and currently, several studies have been pub- lished on the efficacy and safety of ERT in Pompe disease. Clinical studies in infants have shown that ERT led to im- provement in skeletal and cardiac muscle function and to increased survival in many patients (10). As far as the effects of this treatment in older children and adults is concemed, data were available only for a limited number of patients 771