{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:05:47Z","timestamp":1764374747274,"version":"3.46.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Late-onset Pompe\u2019s disease (LOPD) is a progressive treatable metabolic myopathy due to partial acid \u03b1-glucosidase (GAA) deficiency, with potential onset during the pediatric age. To date, Pompe\u2019s disease is not widely included in newborn screening panels, so that clinical suspect remains essential for timely diagnosis and management. Clinical identification of LOPD was shown to be challenging in adult patients, whereas data in children and adolescents are scanty. We conducted an Italian nationwide multicentric survey in order to delineate the characteristics of LOPD in the pediatric population. This prompted us to propose a diagnostic algorithm to facilitate the identification of LOPD in pediatrics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The survey provided information on 38 Italian pediatric patients with a definite biochemical and molecular diagnosis of LOPD firstly suspected based on clinical approach. Nineteen patients (50%) reached medical attention because of clinical symptoms of LOPD (79% within 3 years of age; 21% at 3\u201318 years of age) and 19 (50%) because of incidental finding of asymptomatic hyperCKemia. All the 38 LOPD patients showed hyperCKemia (56%: range 500\u20131000 U\/l; 18%; range 250\u2013500 U\/l; 18% range 1000\u20132000 U\/l; 8% &gt;2000 U\/l), almost invariably accompained by concomitant hypertransaminasemia (91%). Main clinical symptoms before 3 years of age were inability to (1) sit at 8 months, (2) walk indipendently at 18 months, and (3) climb stairs at 30 months. Later pediatric presentations (3\u201318 years of age) were limitation to (1) get up from supine position, (2) perform sport activity, and (3) run. In symptomatic patients, diagnostic latency (i.e. the time interval between clinical onset and diagnosis of LOPD) ranged from &lt;\u20091 year (58%) to 2\u201312 years (42%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Clinical diagnosis of LOPD in pediatrics is challenging in spite of its frequent presentation within 3 years of age. A selective screening by measuring GAA activity on dried blood spot in the two main clinical diagnostic contexts of LOPD in pediatrics \u2013 namely (1) age-related myopathic symptoms or (2) asymptomatic hyperCKemia (and hypertransaminasemia) \u2013 will likely ensure diagnostic anticipation for those patients not screened for Pompe\u2019s disease in the neonatal period.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-025-04063-x","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T11:40:35Z","timestamp":1764330035000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Late-onset Pompe\u2019s disease in pediatrics: results from an Italian national survey on 38 patients and proposal of a targeted diagnostic algorithm"],"prefix":"10.1186","volume":"20","author":[{"given":"Marco","family":"Spada","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Gasperini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimiliano","family":"Filosto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guja","family":"Astrea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Bracci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Bruno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Burlina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Cavallini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Concolino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viola","family":"Crescitelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adele","family":"D\u2019Amico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Deodato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Dionisi-Vici","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Alice","family":"Donati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Fecarotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Fischetto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agata","family":"Fiumara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Furlan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenza","family":"Gragnaniello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damiano","family":"Mala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Marica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Menni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Pagliardini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Panicucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giancarlo","family":"Parenti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Pession","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Ricci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Rovelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Sacchini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo Maria","family":"Santorelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Scarpa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Taurisano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albina","family":"Tummolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-4867","authenticated-orcid":false,"given":"Francesco","family":"Porta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"4063_CR1","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.1002\/humu.23878","volume":"40","author":"AJJ Reuser","year":"2019","unstructured":"Reuser AJJ, van der Ploeg AT, Chien YH, Llerena J Jr, Abbott MA, Clemens PR, Kimonis VE, et al. GAA variants and phenotypes among 1,079 patients with Pompe disease: Data from the Pompe Registry. Hum Mutat. 2019;40:2146\u20134.","journal-title":"Hum Mutat"},{"issue":"9646","key":"4063_CR2","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1016\/S0140-6736(08)61555-X","volume":"372","author":"AT van der Ploeg","year":"2008","unstructured":"van der Ploeg AT, Reuser AJ. Pompe\u2019s disease. Lancet. 2008;372(9646):1342\u201353.","journal-title":"Lancet"},{"key":"4063_CR3","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1212\/01.wnl.0000251268.41188.04","volume":"68","author":"PS Kishnani","year":"2007","unstructured":"Kishnani PS, Corzo D, Nicolino M, Byrne B, Mandel H, Hwu WL, et al. Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology. 2007;68:99\u2013109.","journal-title":"Neurology"},{"key":"4063_CR4","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1515\/jpem-2018-0336","volume":"31","author":"M Spada","year":"2018","unstructured":"Spada M, Pagliardini V, Ricci F, Biamino E, Mongini T, Porta F. Early higher dosage of alglucosidase alpha in classic Pompe disease. J Pediatr Endocrinol Metab. 2018;31:1343\u20137.","journal-title":"J Pediatr Endocrinol Metab"},{"key":"4063_CR5","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1056\/NEJMoa0909859","volume":"362","author":"AT van der Ploeg","year":"2010","unstructured":"van der Ploeg AT, Clemens PR, Corzo D, Escolar DM, Florence J, Groeneveld GJ, et al. A randomized study of alglucosidase alfa in late-onset Pompe\u2019s disease. N Engl J Med. 2010;362:1396\u2013406.","journal-title":"N Engl J Med"},{"key":"4063_CR6","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1016\/S1474-4422(21)00241-6","volume":"20","author":"J Diaz-Manera","year":"2021","unstructured":"Diaz-Manera J, Kishnani PS, Kushlaf H, Ladha S, Mozaffar T, Straub V, et al. Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial. Lancet Neurol. 2021;20:1012\u201326.","journal-title":"Lancet Neurol"},{"key":"4063_CR7","doi-asserted-by":"publisher","first-page":"e39","DOI":"10.1542\/peds.2007-2222","volume":"122","author":"YH Chien","year":"2008","unstructured":"Chien YH, Chiang SC, Zhang XK, Keutzer J, Lee NC, Huang AC, et al. Early detection of Pompe disease by newborn screening is feasible: results from the Taiwan screening program. Pediatrics. 2008;122:e39\u201345.","journal-title":"Pediatrics"},{"issue":"9813","key":"4063_CR8","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/S0140-6736(11)61266-X","volume":"379","author":"TP Mechtler","year":"2012","unstructured":"Mechtler TP, Stary S, Metz TF, De Jes\u00fas VR, Greber-Platzer S, Pollak A, et al. Neonatal screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in Austria. Lancet. 2012;379(9813):335\u201341.","journal-title":"Lancet"},{"key":"4063_CR9","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/s10038-019-0603-7","volume":"64","author":"K Momosaki","year":"2019","unstructured":"Momosaki K, Kido J, Yoshida S, Sugawara K, Miyamoto T, Inoue T, et al. Newborn screening for Pompe disease in Japan: report and literature review of mutations in the GAA gene in Japanese and Asian patients. J Hum Genet. 2019;64:741\u201355.","journal-title":"J Hum Genet"},{"key":"4063_CR10","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3390\/ijns6010004","volume":"6","author":"BK Burton","year":"2020","unstructured":"Burton BK, Charrow J, Hoganson GE, Fleischer J, Grange DK, Braddock SR, et al. Newborn screening for Pompe disease in illinois: experience with 684,290 infants. Int J Neonatal Screen. 2020;6:4.","journal-title":"Int J Neonatal Screen"},{"key":"4063_CR11","doi-asserted-by":"crossref","unstructured":"Gragnaniello V, Pijnappel PWWM, \u2018t Burlina AP et al. Groen SLM, Gueraldi D, Cazzorla C, et al. Newborn screening for Pompe disease in Italy: long-term results and future challenges. Mol Genet Metab Rep. 2022;33:100929.","DOI":"10.1016\/j.ymgmr.2022.100929"},{"key":"4063_CR12","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.ymgme.2013.03.002","volume":"109","author":"M Spada","year":"2013","unstructured":"Spada M, Porta F, Vercelli L, Pagliardini V, Chiad\u00f2-Piat L, Boffi P, et al. Screening for later-onset pompe\u2019s disease in patients with paucisymptomatic hyperckemia. Mol Genet Metab. 2013;109:171\u20133.","journal-title":"Mol Genet Metab"},{"key":"4063_CR13","first-page":"5","volume":"87","author":"O Musumeci","year":"2016","unstructured":"Musumeci O, la Marca G, Spada M, Mondello S, Danesino C, Comi GP, et al. LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population. J Neurol Neurosurg Psychiatry. 2016;87:5\u201311.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"4063_CR14","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s13023-016-0442-y","volume":"11","author":"CI van Capelle","year":"2016","unstructured":"van Capelle CI, van der Meijden JC, van den Hout JM, Jaeken J, Baethmann M, Voit T, et al. Childhood Pompe disease: clinical spectrum and genotype in 31 patients. Orphanet J Rare Dis. 2016;11:65.","journal-title":"Orphanet J Rare Dis"},{"key":"4063_CR15","doi-asserted-by":"crossref","unstructured":"Lee NC, Chang KL, In 't Groen SLM, de Faria DOS, Huang HJ, Pijnappel WWMP, et al. Outcome of later-onset Pompe disease identified through newborn screening. J Pediatr. 2022;244:139\u2009\u2013\u200947.e2.","DOI":"10.1016\/j.jpeds.2021.12.072"},{"key":"4063_CR16","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.ymgme.2012.10.001","volume":"107","author":"M Spada","year":"2012","unstructured":"Spada M, Garelli D, Riggi C, Pagliardini V, Lualdi S, Filocamo M, et al. Spontaneous regression of hypertrophic cardiomyopathy in an infant with pompe\u2019s disease. Mol Genet Metab. 2012;107:763.","journal-title":"Mol Genet Metab"},{"issue":"2","key":"4063_CR17","doi-asserted-by":"publisher","first-page":"362","DOI":"10.3390\/genes14020362","volume":"14","author":"M Faraguna","year":"2023","unstructured":"Faraguna M, Fornari A, Barzaghi S, Savasta S, Foiadelli T, Veraldi D, et al. Treatment dilemma in children with Late-Onset Pompe disease. Genes. 2023;14(2):362.","journal-title":"Genes"},{"key":"4063_CR18","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.1002\/ajmg.a.36110","volume":"161A","author":"PS Kishnani","year":"2013","unstructured":"Kishnani PS, Amartino HM, Lindberg C, Miller TM, Wilson A, Keutzer J. Timing of diagnosis of patients with Pompe disease: data from the Pompe registry. Am J Med Genet A. 2013;161A:2431\u201343.","journal-title":"Am J Med Genet A"},{"key":"4063_CR19","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/1750-1172-7-88","volume":"7","author":"NA van der Beek","year":"2012","unstructured":"van der Beek NA, de Vries JM, Hagemans ML, Hop WC, Kroos MA, Wokke JH, et al. Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study. Orphanet J Rare Dis. 2012;7:88.","journal-title":"Orphanet J Rare Dis"},{"key":"4063_CR20","doi-asserted-by":"crossref","unstructured":"Jiao K, Dong J, Luo S, Yu L, Ke Q, Wang Z, et al. High-risk screening of late-onset Pompe disease: a different early portrait in China. Front Neurol. 2022;965207.","DOI":"10.3389\/fneur.2022.965207"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04063-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-025-04063-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04063-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:03:22Z","timestamp":1764374602000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-025-04063-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,28]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4063"],"URL":"https:\/\/doi.org\/10.1186\/s13023-025-04063-x","relation":{},"ISSN":["1750-1172"],"issn-type":[{"type":"electronic","value":"1750-1172"}],"subject":[],"published":{"date-parts":[[2025,11,28]]},"assertion":[{"value":"26 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human ethics and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"616"}}