{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:23:13Z","timestamp":1790677393286,"version":"4.1.0"},"reference-count":25,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Little is known about clinical symptomatology and genetics of juvenile onset Pompe disease (JOPD). The aims of this study were to analyze how these children are diagnosed, what clinical problems they have, and how phenotype is related to genotype. To accomplish this, we analyzed retrospectively data of 34 patients diagnosed after their first and before completion of their 18th birthday. Median age at diagnosis was 3.9 (range 1.1\u201317) years. Eight patients (23.5%) developed initial symptoms in the first year, 12 (35%) between 1 and 7 years, and 6 (18%) thereafter. Eight (23.5%) had no clinical symptoms at the time of diagnosis. Indications for diagnostics were a positive family history in three (9%), hyperCKemia in eight (23.5%), motor developmental delay in three (9%), and muscle weakness and\/or pain in 17 (50%). Rare clinical signs were failure to thrive, recurrent diarrhea, and suspected hepatopathy with glycogen storage. Thirty-two different mutations were identified. Twenty-seven patients (79.5%) carried the milder c.32\u201313T\u2009&gt;\u2009G mutation, known to be associated with a broad range of phenotypes. Three out of eight patients manifesting within the first year of life showed generalized muscle weakness, hypertrophic cardiomyopathy, and had to be ventilated during the course of disease, thereby demonstrating clinical overlap with infantile onset Pompe disease.<\/jats:p><jats:p>These findings demonstrate that the phenotype of JOPD is broad and that the differential is not only restricted to neuromuscular disorders. Genotypic analysis was useful to delineate subjects with early onset JOPD from those with IOPD, but overall genotype\u2013phenotype correlation was poor.<\/jats:p>","DOI":"10.1055\/s-0041-1735250","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T23:52:12Z","timestamp":1638402732000},"page":"039-045","source":"Crossref","is-referenced-by-count":8,"title":["Clinical and Genetic Aspects of Juvenile Onset Pompe Disease"],"prefix":"10.1055","volume":"53","author":[{"given":"Johanna","family":"Holzwarth","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Justus-Liebig University Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Minopoli","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Justus-Liebig University Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Pfrimmer","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Justus-Liebig University Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Smitka","sequence":"additional","affiliation":[{"name":"Children's hospital, Medical Faculty Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Borrel","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janbernd","family":"Kirschner","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Muschol","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia B.","family":"Hennermann","sequence":"additional","affiliation":[{"name":"Villa Metabolica, Department of Pediatric and Adolescent Medicine, University Medical Center Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd A.","family":"Neubauer","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Justus-Liebig University Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Hobbiebrunken","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center G\u00f6ttingen, Georg August University, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0798-6346","authenticated-orcid":false,"given":"Ralf A.","family":"Husain","sequence":"additional","affiliation":[{"name":"Centre for Inborn Metabolic Disorders, Department of Neuropediatrics, Jena University Hospital, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Justus-Liebig University Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/S0140-6736(08)61555-X","article-title":"Pompe's disease","volume":"372","author":"A T van der Ploeg","year":"2008","journal-title":"Lancet"},{"issue":"13","key":"ref2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.21037\/atm.2019.04.70","article-title":"Long-term outcome and unmet needs in infantile-onset Pompe disease","volume":"7","author":"A Hahn","year":"2019","journal-title":"Ann Transl Med"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1055\/a-1110-7335","article-title":"Diagnosis and care of infants and children with Pompe disease","volume":"232","author":"A Hahn","year":"2020","journal-title":"Klin Padiatr"},{"issue":"02","key":"ref4","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1212\/01.wnl.0000251268.41188.04","article-title":"Recombinant human acid [\u03b1]-glucosidase: major clinical benefits in infantile-onset Pompe disease","volume":"68","author":"P S Kishnani","year":"2007","journal-title":"Neurology"},{"issue":"06","key":"ref5","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1007\/s10545-018-0166-3","article-title":"Long-term follow-up of 17 patients with childhood Pompe disease treated with enzyme replacement therapy","volume":"41","author":"J C van der Meijden","year":"2018","journal-title":"J Inherit Metab Dis"},{"issue":"15","key":"ref6","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1056\/NEJMoa0909859","article-title":"A randomized study of alglucosidase alfa in late-onset Pompe's disease","volume":"362","author":"A T van der Ploeg","year":"2010","journal-title":"N Engl J Med"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13023-016-0442-y","article-title":"Childhood Pompe disease: clinical spectrum and genotype in 31 patients","volume":"11","author":"C I van Capelle","year":"2016","journal-title":"Orphanet J Rare Dis"},{"issue":"06","key":"ref8","doi-asserted-by":"crossref","first-page":"E13","DOI":"10.1002\/humu.20745","article-title":"Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating","volume":"29","author":"M Kroos","year":"2008","journal-title":"Hum Mutat"},{"issue":"02","key":"ref9","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1067\/mpd.2000.107112","article-title":"Identification of two subtypes of infantile acid maltase deficiency","volume":"137","author":"A E Slonim","year":"2000","journal-title":"J Pediatr"},{"issue":"07","key":"ref10","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/s41436-020-0790-9","article-title":"A highly multiplexed biochemical assay for analytes in dried blood spots: application to newborn screening and diagnosis of lysosomal storage disorders and other inborn errors of metabolism","volume":"22","author":"X Hong","year":"2020","journal-title":"Genet Med"},{"issue":"03","key":"ref11","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1212\/WNL.0000000000002758","article-title":"Prevalence of Pompe disease in 3,076 patients with hyperCKemia and limb-girdle muscular weakness","volume":"87","author":"Z Lukacs","year":"2016","journal-title":"Neurology"},{"issue":"11","key":"ref12","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.nmd.2016.09.001","article-title":"The frequency of late-onset Pompe disease in pediatric patients with limb-girdle muscle weakness and nonspecific hyperCKemia: a multicenter study","volume":"26","author":"O \u00dcnver","year":"2016","journal-title":"Neuromuscul Disord"},{"issue":"07","key":"ref13","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.nmd.2018.03.011","article-title":"Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease","volume":"28","author":"M Savarese","year":"2018","journal-title":"Neuromuscul Disord"},{"key":"ref14","first-page":"CD011539","article-title":"Enzyme replacement therapy for infantile-onset Pompe disease","volume":"11","author":"M Chen","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"issue":"03","key":"ref15","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","author":"C M van Gelder","year":"2016","journal-title":"J Inherit Metab Dis"},{"issue":"04","key":"ref16","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","author":"L E Case","year":"2015","journal-title":"Neuromuscul Disord"},{"issue":"02","key":"ref17","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","author":"A K Desai","year":"2018","journal-title":"Mol Genet Metab"},{"issue":"06","key":"ref18","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1111\/ene.13285","article-title":"European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease: a 10-year experience","volume":"24","author":"A T van der Ploeg","year":"2017","journal-title":"Eur J Neurol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.ebiom.2019.03.048","article-title":"A genetic modifier of symptom onset in Pompe disease","volume":"43","author":"A J Bergsma","year":"2019","journal-title":"EBioMedicine"},{"issue":"02","key":"ref20","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1212\/01.wnl.0000252798.25690.76","article-title":"Broad spectrum of Pompe disease in patients with the same c.-32-13T->G haplotype","volume":"68","author":"M A Kroos","year":"2007","journal-title":"Neurology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/1750-1172-8-182","article-title":"Phenotypical variation within 22 families with Pompe disease","volume":"8","author":"S C Wens","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1002\/humu.23854","article-title":"Extension of the Pompe mutation database by linking disease-associated variants to clinical severity","volume":"40","author":"M Y Ni\u00f1o","year":"2019","journal-title":"Hum Mutat"},{"issue":"02","key":"ref23","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/nar\/gkt987","article-title":"Functional characterization of the common c.-32-13T>G mutation of GAA gene: identification of potential therapeutic agents","volume":"42","author":"A Dardis","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"ref24","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1002\/humu.23878","article-title":"GAA variants and phenotypes among 1,079 patients with Pompe disease: data from the Pompe Registry","volume":"40","author":"A JJ Reuser","year":"2019","journal-title":"Hum Mutat"},{"issue":"10","key":"ref25","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1002\/ajmg.a.36110","article-title":"Timing of diagnosis of patients with Pompe disease: data from the Pompe registry","volume":"161A","author":"P S Kishnani","year":"2013","journal-title":"Am J Med Genet A"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0041-1735250.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T13:18:01Z","timestamp":1699881481000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1735250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,1]]},"references-count":25,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2022,1,24]]},"published-print":{"date-parts":[[2022,2]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0041-1735250","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,1]]}}}