{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:16:36Z","timestamp":1789161396032,"version":"build-2803163510"},"reference-count":50,"publisher":"Walter de Gruyter GmbH","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,19]]},"abstract":"Abstract<\/jats:title>\n\nBackground<\/jats:title>\nWith conventional enzyme replacement therapy (ERT), the clinical prognosis of classic Pompe disease is often unsatisfactory. About half the patients treated with ERT at the recommended dosage (20 mg\/kg every other week) require ventilatory support within the first years of life. The heterogeneous response to ERT has been related to different factors, including cross-reactive immunologic material (CRIM) status and age at ERT initiation. Early treatment with a standard dosage of ERT improves clinical outcome and avoids mechanical ventilation in CRIM-positive patients detected at newborn screening, not preventing persistent hyperCKemia and muscle weakness. Later treatment with higher dosages of ERT was shown to provide similar benefits in CRIM-positive patients. Here, we report the clinical and biochemical outcomes of six patients with classic Pompe disease treated with different dosages of alglucosidase alpha at different ages.<\/jats:p><\/jats:sec>\n\nMethods<\/jats:title>\nA standard dosage of ERT was employed in five patients, sharing a poor prognosis after transient clinical improvements, even in the case of early treatment (four died at 22.2\u00b111.9 months and one survived but required tracheostomy and gastrostomy). Early higher dosage of alglucosidase alpha (40 mg\/kg\/week from 14 days) was administered to one CRIM-positive patient with fetal persistent bradycardia.<\/jats:p><\/jats:sec>\n\nResults<\/jats:title>\nEarly higher dosage of alclucosidase alpha not only achieved normal neuromotor development but also the full correction of biochemical markers of muscle damage until 3 years of age, an unmet target with the standard dosage. Speech delay was not prevented by this approach.<\/jats:p><\/jats:sec>\n\nConclusions<\/jats:title>\nWe suggest that early treatment with a higher dosage of ERT may further improve clinical prognosis in classic Pompe disease.<\/jats:p><\/jats:sec>","DOI":"10.1515\/jpem-2018-0336","type":"journal-article","created":{"date-parts":[[2018,11,16]],"date-time":"2018-11-16T04:54:34Z","timestamp":1542344074000},"page":"1343-1347","source":"Crossref","is-referenced-by-count":22,"title":["Early higher dosage of alglucosidase alpha in classic Pompe disease"],"prefix":"10.1515","volume":"31","author":[{"given":"Marco","family":"Spada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Pagliardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Ricci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Biamino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Mongini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Porta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","reference":[{"key":"ref361","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/gim.2011.4","article-title":"Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease","volume":"14","year":"2012","journal-title":"Genet Med"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1542\/peds.2007-2222","article-title":"Early detection of Pompe disease by newborn screening is feasible: results from the Taiwan screening program","volume":"122","year":"2008","journal-title":"Pediatrics"},{"key":"ref371","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s10545-015-9912-y","article-title":"Effects of a higher dose of alglucosidase alfa on ventilator-free survival and motor outcome in classic infantile Pompe disease: an open-label single-center study","volume":"39","year":"2016","journal-title":"J Inherit Metab Dis"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1002\/humu.22108","article-title":"Update of the Pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants","volume":"33","year":"2012","journal-title":"Hum Mutat"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1002\/humu.22108","article-title":"Update of the Pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants","volume":"33","year":"2012","journal-title":"Hum Mutat"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/mus.24522","article-title":"Playing competitive basketball in face of late-onset Pompe disease","volume":"51","year":"2015","journal-title":"Muscle Nerve"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jpeds.2017.11.046","article-title":"High sustained antibody titers in patients with classic infantile Pompe disease following immunomodulation at start of enzyme replacement therapy","volume":"195","year":"2018","journal-title":"J Pediatr"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13023-018-0771-0","article-title":"Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy","volume":"13","year":"2018","journal-title":"Orphanet J Rare Dis"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgmr.2018.05.002","article-title":"Pompe disease treatment with twice a week high dose alglucoside alfa in a patient with severe dilated cardiomyopathy","volume":"16","year":"2018","journal-title":"Mol Genet Metab Rep"},{"key":"ref321","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1212\/01.wnl.0000251268.41188.04","article-title":"Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe 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Pediatr"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1212\/01.wnl.0000251268.41188.04","article-title":"Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease","volume":"68","year":"2007","journal-title":"Neurology"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jpeds.2015.10.078","article-title":"Very early treatment for infantile-onset Pompe disease contributes to better outcomes","volume":"169","year":"2016","journal-title":"J Pediatr"},{"key":"ref491","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.ejpn.2016.12.004","article-title":"Longitudinal follow-up to evaluate speech disorders in early-treated patients with infantile-onset Pompe disease","volume":"21","year":"2017","journal-title":"Eur J Paediatr Neurol"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.nmd.2014.12.004","article-title":"Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease","volume":"25","year":"2015","journal-title":"Neuromuscul Disord"},{"key":"ref51","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","year":"2010","journal-title":"N Engl J Med"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ymgme.2013.03.002","article-title":"Screening for later-onset Pompe\u2019s disease in patients with paucisymptomatic hyperCKemia","volume":"109","year":"2013","journal-title":"Mol Genet Metab"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.nmd.2014.12.004","article-title":"Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease","volume":"25","year":"2015","journal-title":"Neuromuscul Disord"},{"key":"ref251","first-page":"1342","article-title":"Lysosomal storage disease 2 \u2013 Pompe\u2019s disease","volume":"372","year":"2008","journal-title":"Lancet"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"S333","DOI":"10.1007\/s10545-010-9179-2","article-title":"Antenatal diagnosis of Pompe disease by fetal echocardiography: impact on outcome after early initiation of enzyme replacement therapy","volume":"33","year":"2010","journal-title":"J Inherit Metab Dis"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.ejpn.2016.12.004","article-title":"Longitudinal follow-up to evaluate speech disorders in early-treated patients with infantile-onset Pompe disease","volume":"21","year":"2017","journal-title":"Eur J Paediatr Neurol"},{"key":"ref301","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","year":"2010","journal-title":"N Engl J 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Fail"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.nmd.2009.11.014","article-title":"The Children\u2019s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): test development and reliability","volume":"20","year":"2010","journal-title":"Neuromuscul Disord"},{"key":"ref01","first-page":"1342","article-title":"Lysosomal storage disease 2 \u2013 Pompe\u2019s disease","volume":"372","year":"2008","journal-title":"Lancet"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13023-018-0771-0","article-title":"Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy","volume":"13","year":"2018","journal-title":"Orphanet J Rare Dis"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/gim.2011.4","article-title":"Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease","volume":"14","year":"2012","journal-title":"Genet Med"},{"key":"ref291","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1542\/peds.2007-2222","article-title":"Early detection of Pompe disease by newborn screening is feasible: results from the Taiwan screening program","volume":"122","year":"2008","journal-title":"Pediatrics"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ymgme.2017.12.435","article-title":"Enzyme replacement therapy with alglucosidase alfa in Pompe disease: clinical experience with rate escalation","volume":"123","year":"2018","journal-title":"Mol Genet Metab"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jpeds.2005.11.033","article-title":"A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease","volume":"148","year":"2006","journal-title":"J Pediatr"},{"key":"ref141","first-page":"40","article-title":"Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: lessons learned from 10 years of clinical laboratory testing experience","volume":"160","year":"2012","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.jpeds.2014.10.068","article-title":"Long-term prognosis of patients with infantile-onset Pompe disease diagnosed by newborn screening and treated since birth","volume":"166","year":"2015","journal-title":"J Pediatr"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ymgme.2013.03.002","article-title":"Screening for later-onset Pompe\u2019s disease in patients with paucisymptomatic hyperCKemia","volume":"109","year":"2013","journal-title":"Mol Genet Metab"},{"key":"ref411","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.nmd.2009.11.014","article-title":"The Children\u2019s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): test development and reliability","volume":"20","year":"2010","journal-title":"Neuromuscul Disord"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.ymgme.2012.10.001","article-title":"Spontaneous regression of hypertrophic cardiomyopathy in an infant with Pompe\u2019s disease","volume":"107","year":"2012","journal-title":"Mol Genet Metab"},{"key":"ref441","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ymgme.2017.12.435","article-title":"Enzyme replacement therapy with alglucosidase alfa in Pompe disease: clinical experience with rate escalation","volume":"123","year":"2018","journal-title":"Mol Genet Metab"},{"key":"ref481","doi-asserted-by":"crossref","first-page":"S333","DOI":"10.1007\/s10545-010-9179-2","article-title":"Antenatal diagnosis of Pompe disease by fetal echocardiography: impact on outcome after early initiation of enzyme replacement therapy","volume":"33","year":"2010","journal-title":"J Inherit Metab Dis"},{"key":"ref391","first-page":"40","article-title":"Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: lessons learned from 10 years of clinical laboratory testing experience","volume":"160","year":"2012","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"ref471","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jpeds.2017.11.046","article-title":"High sustained antibody titers in patients with classic infantile Pompe disease following immunomodulation at start of enzyme replacement therapy","volume":"195","year":"2018","journal-title":"J Pediatr"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/mus.24522","article-title":"Playing competitive basketball in face of late-onset Pompe disease","volume":"51","year":"2015","journal-title":"Muscle Nerve"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.jpeds.2014.10.068","article-title":"Long-term prognosis of patients with infantile-onset Pompe disease diagnosed by newborn screening and treated since birth","volume":"166","year":"2015","journal-title":"J Pediatr"},{"key":"ref211","article-title":"Sustained immune tolerance induction in enzyme replacement therapy-treated CRIM-negative patients with infantile Pompe disease","volume":"2","year":"2017","journal-title":"JCI Insight"},{"key":"ref451","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgmr.2018.05.002","article-title":"Pompe disease treatment with twice a week high dose alglucoside alfa in a patient with severe dilated cardiomyopathy","volume":"16","year":"2018","journal-title":"Mol Genet Metab Rep"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s10545-015-9912-y","article-title":"Effects of a higher dose of alglucosidase alfa on ventilator-free survival and motor outcome in classic infantile Pompe disease: an open-label single-center study","volume":"39","year":"2016","journal-title":"J Inherit Metab Dis"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.cardfail.2011.07.011","article-title":"Left ventricular geometry, global function, and dyssynchrony in infants and children with Pompe cardiomyopathy undergoing enzyme replacement therapy","volume":"17","year":"2011","journal-title":"J Card Fail"},{"key":"ref461","article-title":"Sustained immune tolerance induction in enzyme replacement therapy-treated CRIM-negative patients with infantile Pompe disease","volume":"2","year":"2017","journal-title":"JCI Insight"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"link":[{"URL":"http:\/\/www.degruyter.com\/view\/j\/jpem.2018.31.issue-12\/jpem-2018-0336\/jpem-2018-0336.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2018-0336\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T01:44:36Z","timestamp":1619055876000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2018-0336\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,19]]},"references-count":50,"journal-issue":{"issue":"12"},"URL":"https:\/\/doi.org\/10.1515\/jpem-2018-0336","relation":{},"ISSN":["2191-0251","0334-018X"],"issn-type":[{"value":"2191-0251","type":"electronic"},{"value":"0334-018X","type":"print"}],"subject":[],"published":{"date-parts":[[2018,12,19]]}}}