{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:48:57Z","timestamp":1768956537675,"version":"3.49.0"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Background and Clinical Significance: Classic infantile-onset Pompe disease (IOPD) is the most severe form of Pompe disease, manifesting within the first months of life with hypertrophic cardiomyopathy and severe hypotonia. Avalglucosidase alfa is a next-generation recombinant human \u03b1-glucosidase that was recently approved for use. Clinical trials, conducted on IOPD patients already treated with alglucosidase alfa, have recommended a dosage ranging from 20 to 40 mg\/kg every other week. The optimal dosage for treatment-na\u00efve patients has not yet been established. We present a case of a severe IOPD patient who received a short-term high-dose, high-frequency regimen of avalglucosidase alfa (40 mg\/kg\/week). Case Presentation: The patient, a 3-month-old infant, presented with hypotonia and severe hypertrophic cardiomyopathy (left ventricular mass index (LVMI) of 136 g\/m2; ejection fraction (EF) of 60%). Treatment with avalglucosidase alfa was initiated at a dose of 40 mg\/kg every other week. After two weeks, cardiac function further deteriorated (LVMI of 168 g\/m2; EF of 46%), so the treatment was intensified to a dose of 40 mg\/kg weekly for two months. This resulted in significant clinical, biochemical, and motor improvements without adverse reactions. Following this improvement, the dosage of 40 mg\/kg every other week was reinstated. At 18 months of age, the patient demonstrated normal motor development, normal cardiac function (LVMI of 49 g\/m2; EF of 68%), and normal biomarkers. Conclusions: Although limited to a single patient, this case illustrates that short-term high-dose, high-frequency administration of avalglucosidase alfa could be both effective and safe, even in patients with severe, late-diagnosed IOPD.<\/jats:p>","DOI":"10.3390\/reports9010031","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T11:27:58Z","timestamp":1768908478000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Short-Term Intensive Avalglucosidase Alfa Regimen in Late-Diagnosed Infantile Pompe Disease: A Case Report"],"prefix":"10.3390","volume":"9","author":[{"given":"Vincenza","family":"Gragnaniello","sequence":"first","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Department of Woman\u2019s and Child\u2019s Health, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4799-5551","authenticated-orcid":false,"given":"Alice","family":"Pozza","sequence":"additional","affiliation":[{"name":"Paediatric Cardiology Unit, Department of Woman\u2019s and Child\u2019s Health, University of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8081-3997","authenticated-orcid":false,"given":"Chiara","family":"Cazzorla","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Department of Woman\u2019s and Child\u2019s Health, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Gueraldi","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Department of Woman\u2019s and Child\u2019s Health, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-0113","authenticated-orcid":false,"given":"Giovanni","family":"Di Salvo","sequence":"additional","affiliation":[{"name":"Paediatric Cardiology Unit, Department of Woman\u2019s and Child\u2019s Health, University of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7724-137X","authenticated-orcid":false,"given":"Alberto B.","family":"Burlina","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Department of Woman\u2019s and Child\u2019s Health, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1186\/s13023-024-03373-w","article-title":"The European Reference Network for Metabolic Diseases (MetabERN) Clinical Pathway Recommendations for Pompe Disease (Acid Maltase Deficiency, Glycogen Storage Disease Type II)","volume":"19","author":"Parenti","year":"2024","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/S0140-6736(08)61555-X","article-title":"Pompe\u2019s disease","volume":"372","author":"Reuser","year":"2008","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jpeds.2019.08.058","article-title":"Clinical and Molecular Disease Spectrum and Outcomes in Patients with Infantile-Onset Pompe Disease","volume":"216","author":"Gupta","year":"2020","journal-title":"J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S2352-4642(21)00308-4","article-title":"Effect of Alglucosidase Alfa Dosage on Survival and Walking Ability in Patients with Classic Infantile Pompe Disease: A Multicentre Observational Cohort Study from the European Pompe Consortium","volume":"6","author":"Ditters","year":"2022","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_5","first-page":"100929","article-title":"Newborn Screening for Pompe Disease in Italy: Long-Term Results and Future Challenges","volume":"33","author":"Gragnaniello","year":"2022","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1136\/jmg-2022-108675","article-title":"Long-term outcomes of very early treated infantile-onset Pompe disease with short-term steroid premedication: Experiences from a nationwide newborn screening programme","volume":"60","author":"Yang","year":"2023","journal-title":"J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1203\/PDR.0b013e3181b24e94","article-title":"Early Treatment With Alglucosidase Alfa Prolongs Long-Term Survival of Infants With Pompe Disease","volume":"66","author":"Kishnani","year":"2009","journal-title":"Pediatr. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ymgme.2009.08.003","article-title":"Cross-Reactive Immunologic Material Status Affects Treatment Outcomes in Pompe Disease Infants","volume":"99","author":"Kishnani","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41436-020-01080-y","article-title":"Transforming the Clinical Outcome in CRIM-Negative Infantile Pompe Disease Identified via Newborn Screening: The Benefits of Early Treatment with Enzyme Replacement Therapy and Immune Tolerance Induction","volume":"23","author":"Li","year":"2021","journal-title":"Genet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13052-022-01219-4","article-title":"Immune Responses to Alglucosidase in Infantile Pompe Disease: Recommendations from an Italian Pediatric Expert Panel","volume":"48","author":"Gragnaniello","year":"2022","journal-title":"Ital. J. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1007\/s40265-021-01600-3","article-title":"Avalglucosidase Alfa: First Approval","volume":"81","author":"Dhillon","year":"2021","journal-title":"Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.nmd.2018.12.004","article-title":"Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of the Novel Enzyme Replacement Therapy Avalglucosidase Alfa (neoGAA) in Treatment-Na\u00efve and Alglucosidase Alfa-Treated Patients with Late-Onset Pompe Disease: A Phase 1, Open-Label, Multicenter, Multinational, Ascending Dose Study","volume":"29","author":"Pena","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/mt.2009.37","article-title":"Glycoengineered Acid \u03b1-Glucosidase With Improved Efficacy at Correcting the Metabolic Aberrations and Motor Function Deficits in a Mouse Model of Pompe Disease","volume":"17","author":"Zhu","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1002\/jimd.12543","article-title":"Regulatory News: Avalglucosidase Alfa-Ngpt (Nexviazyme) for Late-Onset Pompe Disease-FDA Approval Summary","volume":"45","author":"Punnoose","year":"2022","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1515\/jpem-2018-0336","article-title":"Early higher dosage of alglucosidase alpha in classic Pompe disease","volume":"31","author":"Spada","year":"2018","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.echo.2020.09.019","article-title":"Pediatric Heart Network Echocardiographic Z Scores: Comparison with Other Published Models","volume":"34","author":"Lopez","year":"2021","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/s41436-018-0270-7","article-title":"An Immune Tolerance Approach Using Transient Low-Dose Methotrexate in the ERT-Na\u00efve Setting of Patients Treated with a Therapeutic Protein: Experience in Infantile-Onset Pompe Disease","volume":"21","author":"Kazi","year":"2019","journal-title":"Genet. Med."},{"key":"ref_18","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","author":"Parini","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1116","DOI":"10.1542\/peds.2008-3667","article-title":"Pompe disease in infants: Improving the prognosis by newborn screening and early treatment","volume":"124","author":"Chien","year":"2009","journal-title":"Pediatrics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"985\u2013991.e1\u20132","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","author":"Chien","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100328","DOI":"10.1016\/j.gim.2022.10.010","article-title":"Safety and Efficacy of Avalglucosidase Alfa in Individuals with Infantile-Onset Pompe Disease Enrolled in the Phase 2, Open-Label Mini-COMET Study: The 6-Month Primary Analysis Report","volume":"25","author":"Kishnani","year":"2023","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"114664","DOI":"10.1016\/j.jpeds.2025.114664","article-title":"The Mini-COMET Clinical Trial: Safety and Efficacy of Avalglucosidase Alfa after 97 Weeks of Treatment in Children with Infantile-Onset Pompe Disease Previously Treated with Alglucosidase Alfa","volume":"285","author":"Kronn","year":"2025","journal-title":"J. Pediatr."},{"key":"ref_23","first-page":"101126","article-title":"Avalglucosidase Alfa in Infantile-Onset Pompe Disease: A Snapshot of Real-World Experience in Italy","volume":"40","author":"Fiumara","year":"2024","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101373","DOI":"10.1016\/j.gim.2025.101373","article-title":"Efficacy of transitioning from alglucosidase alfa to avalglucosidase alfa in infantile-onset Pompe disease: A single-center cohort analysis","volume":"27","author":"Chien","year":"2025","journal-title":"Genet. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.jpeds.2009.03.015","article-title":"Reversal of Cardiac Dysfunction after Enzyme Replacement in Patients with Infantile-Onset Pompe Disease","volume":"155","author":"Chen","year":"2009","journal-title":"J. Pediatr."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gragnaniello, V., Rizzardi, C., Commone, A., Gueraldi, D., Maines, E., Salviati, L., Di Salvo, G., and Burlina, A.B. (2023). Unusual Evolution of Hypertrophic Cardiomyopathy in Non-Compaction Myocardium in a Pompe Disease Patient. J. Clin. Med., 12.","DOI":"10.3390\/jcm12062365"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1001\/jamaneurol.2023.0552","article-title":"Efficacy and Safety of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease After 97 Weeks: A Phase 3 Randomized Clinical Trial","volume":"80","author":"Kishnani","year":"2023","journal-title":"JAMA Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kishnani, P.S., Van Den Hout, J.M.P., Hahn, A., Kronn, D., Chien, Y.-H., Han, M., Heuterman, J., Sparks, S., Glen, C., and Daba, N. (2025). Insights into immunogenicity and therapeutic strategies to mitigate the immune response in infantile-onset Pompe disease: A comprehensive systematic literature review. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1690312"}],"container-title":["Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2571-841X\/9\/1\/31\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:05:00Z","timestamp":1768910700000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2571-841X\/9\/1\/31"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["reports9010031"],"URL":"https:\/\/doi.org\/10.3390\/reports9010031","relation":{},"ISSN":["2571-841X"],"issn-type":[{"value":"2571-841X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]}}}