{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:32:16Z","timestamp":1790839936485,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Late-onset Pompe disease (LOPD) is a rare, progressive disorder characterized by limb\u2013girdle muscle weakness and\/or respiratory insufficiency, caused by acid alpha-glucosidase (GAA) gene mutations and treated with enzyme replacement therapy. We studied isometric muscle strength in eight muscle groups bilaterally using a Biodex\u00ae dynamometer, as well as the Medical Research Council sum score (MRC-SS), hand grip strength, 6 min walk distance (6MWD), 10 m walk test (10MWT) and timed up-and-go test (TUG) in 12 adult, ambulatory, treated LOPD patients and 12 age-\/gender-matched healthy controls, every 6 months for 2 years. The mean isometric muscle strength showed a significant decline in right and left knee extensors at 12 months in controls (p &lt; 0.014; p &lt; 0.016), at 18 months in patients (p &lt; 0.010; p &lt; 0.007) and controls (only right side, p &lt; 0.030) and at 24 months in both groups (p &lt; 0.035). The mean 6MWD in patients significantly decreased after 24 months, from 451.9 m to 368.1 m (p &lt; 0.003), whereas in controls, the mean 6MWD significantly increased after 6 months (p &lt; 0.045) and 18 months (p &lt; 0.020) (at 24 months p = 0.054). In patients and controls, the MRC-SS, hand grip test, 10MWT and TUG did not show significant changes (p &gt; 0.05). We conclude that the 6MWD is a useful outcome measure to detect motor decline in treated LOPD patients.<\/jats:p>","DOI":"10.3390\/cells11030334","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T22:40:20Z","timestamp":1642718420000},"page":"334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Six-Minute Walk Distance Is a Useful Outcome Measure to Detect Motor Decline in Treated Late-Onset Pompe Disease Patients"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-443X","authenticated-orcid":false,"given":"Kristl G.","family":"Claeys","sequence":"first","affiliation":[{"name":"Department of Neurology, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"D\u2019Hondt","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8366-0180","authenticated-orcid":false,"given":"Lucas","family":"Fache","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"Peers","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-6557","authenticated-orcid":false,"given":"Christophe E.","family":"Depuydt","sequence":"additional","affiliation":[{"name":"Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21037\/atm.2019.05.29","article-title":"Pompe disease: What are we missing?","volume":"7","author":"Schoser","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"284","DOI":"10.21037\/atm.2019.07.24","article-title":"Multisystem late onset Pompe disease (LOPD): An update on clinical aspects","volume":"7","author":"Toscano","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21037\/atm.2019.04.70","article-title":"Long-term outcome and unmet needs in infantile-onset Pompe disease","volume":"7","author":"Hahn","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_4","first-page":"768.e31","article-title":"European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease: A 10-year experience","volume":"24","author":"Kruijshaar","year":"2017","journal-title":"Eur. J. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1177\/1756285609103324","article-title":"Progress in Enzyme Replacement Therapy in Glycogen Storage Disease Type II","volume":"2","author":"Angelini","year":"2009","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1468-1331.2008.02377.x","article-title":"Glycogen storage disease type II (Pompe disease)\u2014influence of enzyme replacement therapy in adults","volume":"16","author":"Merk","year":"2009","journal-title":"Eur. J. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s10545-010-9201-8","article-title":"Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II","volume":"33","author":"Bembi","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s10545-010-9204-5","article-title":"Changes in skeletal muscle qualities during enzyme replacement therapy in late-onset type II glycogenosis: Temporal and spatial pattern of mass vs. strength response","volume":"33","author":"Ravaglia","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s00415-009-5275-3","article-title":"Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial","volume":"257","author":"Strothotte","year":"2010","journal-title":"J. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.nmd.2010.07.277","article-title":"Effect of enzyme therapy in juvenile patients with Pompe disease: A three-year open-label study","volume":"20","author":"Hagemans","year":"2010","journal-title":"Neuromuscul. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1056\/NEJMoa0909859","article-title":"A randomized study of alglucosidase alfa in late-onset Pompe\u2019s disease","volume":"362","author":"Clemens","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1007\/s00415-011-6293-5","article-title":"Observational clinical study in juvenile-adult glycogenosis type 2 patients undergoing enzyme replacement therapy for up to 4 years","volume":"259","author":"Angelini","year":"2012","journal-title":"J. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.braindev.2011.05.004","article-title":"Close monitoring of initial enzyme replacement therapy in a patient with childhood-onset Pompe disease","volume":"34","author":"Ishigaki","year":"2012","journal-title":"Brain Dev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ymgme.2012.05.016","article-title":"Can genes influencing muscle function affect the therapeutic response to enzyme replacement therapy (ERT) in late-onset type II glycogenosis?","volume":"107","author":"Ravaglia","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s10545-012-9451-8","article-title":"36 months observational clinical study of 38 adult Pompe disease patients under alglucosidase alfa enzyme replacement therapy","volume":"35","author":"Regnery","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.ymgme.2012.09.015","article-title":"Open-label extension study following the Late-Onset Treatment Study (LOTS) of alglucosidase alfa","volume":"107","author":"Barohn","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1007\/s10545-014-9728-1","article-title":"Effectiveness of enzyme replacement therapy in adults with late-onset Pompe disease: Results from the NCS-LSD cohort study","volume":"37","author":"Anderson","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ymgme.2014.02.015","article-title":"Effect of enzyme replacement therapy on isokinetic strength for all major muscle groups in four patients with Pompe disease\u2014A long-term follow-up","volume":"112","author":"Andreassen","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1007\/s00415-015-7664-0","article-title":"Clinical and molecular aspects of 30 patients with late-onset Pompe disease (LOPD): Unusual features and response to treatment","volume":"262","author":"Montagnese","year":"2015","journal-title":"J. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ymgme.2016.05.013","article-title":"Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study","volume":"119","author":"Carlier","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1212\/WNL.0000000000004711","article-title":"Long-term benefit of enzyme replacement therapy in Pompe disease: A 5-year prospective study","volume":"89","author":"Kuperus","year":"2017","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.pjnns.2018.05.002","article-title":"Enzymatic replacement therapy in patients with late-onset Pompe disease\u20146-Year follow up","volume":"52","author":"Witkowski","year":"2018","journal-title":"Neurol. Neurochir. Pol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1002\/jimd.12272","article-title":"Long-term benefit of enzyme replacement therapy with alglucosidase alfa in adults with Pompe disease: Prospective analysis from the French Pompe Registry","volume":"43","author":"Semplicini","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13023-020-01353-4","article-title":"Late-onset Pompe disease (LOPD) in Belgium: Clinical characteristics and outcome measures","volume":"15","author":"Vanherpe","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_25","unstructured":"Buckon, C., Sienko, S., Bagley, A., Sison-Williamson, M., Fowler, E., Staudt, L., Heberer, K., McDonald, C.M., and Sussman, M. (2016). Can Quantitative Muscle Strength and Functional Motor Ability Differentiate the Influence of Age and Corticosteroids in Ambulatory Boys with Duchenne Muscular Dystrophy?. PLoS Curr., 8."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.nmd.2018.06.007","article-title":"A cross-sectional analysis of clinical evaluation in 35 individuals with mutations of the valosin-containing protein gene","volume":"28","author":"Plewa","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0169-2607(95)01703-8","article-title":"MedCalc: A new computer program for medical statistics","volume":"48","author":"Schoonjans","year":"1995","journal-title":"Comput. Methods Programs Biomed."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories (2002). ATS statement: Guidelines for the 6-min walk test. Am. J. Respir. Crit. Care Med., 166, 111\u2013117.","DOI":"10.1164\/ajrccm.166.1.at1102"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1056\/NEJMoa1011367","article-title":"Systemic administration of PRO051 in Duchenne\u2019s muscular dystrophy","volume":"364","author":"Goemans","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/S0140-6736(17)31611-2","article-title":"Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","volume":"390","author":"McDonald","year":"2017","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s00415-020-10223-9","article-title":"Nusinersen treatment significantly improves hand grip strength, hand motor function and MRC sum scores in adult patients with spinal muscular atrophy types 3 and 4","volume":"268","author":"Goosens","year":"2021","journal-title":"J. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1002\/mus.21025","article-title":"Clinical features of late-onset Pompe disease: A prospective cohort study","volume":"38","author":"Wokke","year":"2008","journal-title":"Muscle Nerve"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1183\/09031936.00194909","article-title":"Six Minute Walk Distance Project (ALAT). The 6-min walk distance in healthy subjects: Reference standards from seven countries","volume":"37","author":"Casanova","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e1756","DOI":"10.1212\/WNL.0000000000008441","article-title":"Large variation in effects during 10 years of enzyme therapy in adults with Pompe disease","volume":"93","author":"Harlaar","year":"2019","journal-title":"Neurology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/jep.12629","article-title":"Minimal clinically important difference for change in 6-min walk test distance of adults with pathology: A systematic review","volume":"23","author":"Bohannon","year":"2017","journal-title":"J. Eval. Clin. Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.nmd.2012.10.024","article-title":"The Rasch-built Pompe-specific activity (R-PAct) scale","volume":"23","author":"Hagemans","year":"2013","journal-title":"Neuromuscul. Disord."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1186\/s13023-020-01469-7","article-title":"Positive association between physical outcomes and patient-reported outcomes in late-onset Pompe disease: A cross sectional study","volume":"15","author":"Yuan","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/1750-1172-7-88","article-title":"Clinical features and predictors for disease natural progression in adults with Pompe disease: A nationwide prospective observational study","volume":"7","author":"Hagemans","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/S1474-4422(21)00241-6","article-title":"Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): A phase 3, randomised, multicentre trial","volume":"20","author":"Kishnani","year":"2021","journal-title":"Lancet Neurol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/3\/334\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:04:22Z","timestamp":1760133862000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/3\/334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,20]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cells11030334"],"URL":"https:\/\/doi.org\/10.3390\/cells11030334","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,20]]}}}