{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T19:55:48Z","timestamp":1784836548278,"version":"3.55.0"},"reference-count":106,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clin Med Insights Pediatr"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>Infantile-onset Pompe disease (IOPD) is a rare genetic disorder associated with a deficiency of a lysosomal enzyme, the acid alpha-glucosidase. It is characterized by the accumulation of lysosomal and non-lysosomal-bound glycogen in various organs, such as the heart, skeletal muscle, and brain tissue, resulting in muscle weakness, hypertrophic cardiomyopathy, respiratory insufficiency, and other complications. Without treatment, IOPD has a very high mortality rate, with patients dying within the first year of life. Over the past few decades, significant therapeutic advancements have been made to improve the prognosis and quality of life for IOPD patients. Enzyme replacement therapy (ERT) with recombinant human GAA has been the cornerstone of treatment, demonstrating efficacy in prolonging survival and reducing cardiac hypertrophy. However, ERT has limitations, including the development of immune responses, inconsistent skeletal muscle uptake, and the inability to cross the brain barrier. Recent research has focused on enhancing ERT through adjunctive therapies such as immune modulation, gene therapy, and chaperone-mediated approaches to improve enzyme delivery and function. Additionally, advancements in early diagnosis, including newborn screening, have enabled timely intervention, which is crucial for better outcomes. This review comprehensively examines the current therapeutic strategies for IOPD, their efficacy, challenges, and future directions for managing this disease.<\/jats:p>","DOI":"10.1177\/11795565251337900","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T11:53:06Z","timestamp":1754913186000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Latest Advancements in Treatment Options for Infantile-Onset Pompe Disease: A Comprehensive Narrative Review"],"prefix":"10.1177","volume":"19","author":[{"given":"Misha","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, Liaquat National Hospital and Medical College, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mufliha","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Liaquat National Hospital and Medical College, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhana","family":"Riaz","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Liaquat National Hospital and Medical College, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab","family":"Awan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Liaquat National Hospital and Medical College, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eeshal","family":"Zulfiqar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Kumar","sequence":"additional","affiliation":[{"name":"Medical Research Center, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7740-1453","authenticated-orcid":false,"given":"Ahmed Sermed","family":"Al Sakini","sequence":"additional","affiliation":[{"name":"MBChB, College of Medicine, University of Baghdad, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq Mahmood","family":"Khan","sequence":"additional","affiliation":[{"name":"Clinic Fellow Cardiothoracic Surgery, Golden Jubilee National Hospital, Clydebank, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Saad","family":"Al-shammari","sequence":"additional","affiliation":[{"name":"MBChB, College of Medicine, University of Baghdad, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"issue":"11","key":"e_1_3_3_2_2","article-title":"Navigating Pompe disease assessment: a comprehensive scoping review","volume":"16","author":"Nunes Campos L","year":"2024","unstructured":"Nunes Campos L, Davila Rivera I, Iba\u00f1ez Alegre DM, et al. Navigating Pompe disease assessment: a comprehensive scoping review. Cureus. 2024;16(11):e73593.","journal-title":"Cureus"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108590"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2890681"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4781(87)90064-9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53985-5"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35662"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.04.13"},{"key":"e_1_3_3_9_2","unstructured":"National Organization for Rare Disorders (NORD). Pompe disease. 2021. Accessed February\u200927 2025. https:\/\/rarediseases.org\/rare-diseases\/pompe-disease\/"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.05.29"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31318"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-022-00736-1"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijns6010009"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijns6010004"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijns6040089"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijns6010011"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-02146-z"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2010.11.053"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36197"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1221140"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2024.09.043"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103794"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2023.107650"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.112.2.332"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-35"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.11.39"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/93.3.599"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom10091339"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.02.004"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010383421286"},{"key":"e_1_3_3_31_2","first-page":"132","article-title":"Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I\/II clinical trial","volume":"3","author":"Amalfitano A","year":"2001","unstructured":"Amalfitano A, Bengur AR, Morse RP, et al. Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I\/II clinical trial. Genet Med. 2001;3:132-138.","journal-title":"Genet Med"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2004.10.009"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-837543"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2006.02.035"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000251268.41188.04"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e3181b24e94"},{"issue":"4","key":"e_1_3_3_37_2","first-page":"271","article-title":"Infantile-onset Pompe disease: diagnosis and management [Enfermedad de Pompe infantil: Diagn\u00f3stico y tratamiento]","volume":"117","author":"Bay LB","year":"2019","unstructured":"Bay LB, Denzler I, Durand C, et al. Infantile-onset Pompe disease: diagnosis and management [Enfermedad de Pompe infantil: Diagn\u00f3stico y tratamiento]. Arch Argent Pediatr. 2019;117(4):271-278.","journal-title":"Arch Argent Pediatr"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.10.012"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181a87867"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.gim.0000195896.04069.5f"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-008-9267-3"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.12.004"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0738-0"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(21)00308-4"},{"key":"e_1_3_3_45_2","first-page":"101179","article-title":"Dose-intensive therapy (DIT) for infantile Pompe disease: a pilot study","volume":"42","author":"Jarnes JR","year":"2024","unstructured":"Jarnes JR, Pillai NR, Ahmed A, Shrestha S, Stark M, Whitley CB. Dose-intensive therapy (DIT) for infantile Pompe disease: a pilot study. Mol Genet Metab Rep. 2024;42:101179.","journal-title":"Mol Genet Metab Rep"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.10.016"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc400365a"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.37"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.10.010"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2024.101126"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108608"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01886-5"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph16091199"},{"key":"e_1_3_3_54_2","unstructured":"A study to evaluate the safety efficacy PK PD and immunogenicity of cipaglucosidase Alfa\/Miglustat in IOPD subjects aged 0 to <18 (ROSSELLA). ClinicalTrials.gov Identifier NCT04808505. Last updated November 6 2024. Accessed February 27 2025. https:\/\/clinicaltrials.gov\/study\/NCT04808505"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.10.078"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-3667"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-0280E"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94328"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01727"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2024.101141"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10020302"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2017.06.007"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2002.0580"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2005.01.012"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.3233\/JND-190426"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2014.33"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300100"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.305"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2024.101899"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1089\/humc.2017.146"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2012.250"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1089\/humc.2014.2514"},{"key":"e_1_3_3_73_2","unstructured":"Clinical exploration of adeno-associated virus (AAV) expressing human acid Alpha- glucosidase (GAA) gene therapy for patients with infantile-onset pompe disease. clinicaltrials.gov Identifier NCT05567627. Last updated November 1 2023. Accessed February 27 2024. https:\/\/clinicaltrials.gov\/study\/NCT05567627?cond=Infantile-onset%20Pompe%20Disease&term=type%20II%20glycogen%20storage%20disease&intr=gene%20therapy&rank=2"},{"key":"e_1_3_3_74_2","unstructured":"Evaluation of the safety and efficacy of Infantile-onset Pompe Disease gene therapy drug. ClinicalTrials.gov. Identifier: NCT05793307. Last updated June 6 2023. Accessed February 27 2025. https:\/\/clinicaltrials.gov\/study\/NCT05793307?cond=Infantile-onset%20Pompe%20Disease&term=type%20II%20glycogen%20storage%20disease&intr=gene%20therapy&rank=1&a=3"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.195"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2016.12.010"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2017.12.011"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.04.67"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccas.2024.102446"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.152"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2008.009"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.200900036"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.53"},{"key":"e_1_3_3_84_2","unstructured":"Study to evaluate the safety of AT2220 (Duvoglustat) in Pompe disease. ClinicalTrials.gov. Identifier: NCT00688597. Accessed February 27 2025. https:\/\/clinicaltrials.gov\/study\/NCT00688597?id=%22NCT00688597%22&rank=1"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.138"},{"issue":"9","key":"e_1_3_3_86_2","first-page":"852","article-title":"T.P.45 an ongoing phase 2a study to investigate drug\u2013drug interactions between escalating doses of AT2220 (duvoglustat hydrochloride) and acid alpha glucosidase in subjects with Pompe disease \u2013 preliminary results","volume":"22","author":"Kishnani P","year":"2012","unstructured":"Kishnani P, Tarnopolsky M, Sivakumar K, et al. T.P.45 an ongoing phase 2a study to investigate drug\u2013drug interactions between escalating doses of AT2220 (duvoglustat hydrochloride) and acid alpha glucosidase in subjects with Pompe disease \u2013 preliminary results. Neuromuscul Disord. 2012;22(9\u201310):852.","journal-title":"Neuromuscul Disord"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1002\/iub.529"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn290"},{"key":"e_1_3_3_89_2","unstructured":"A randomized phase 1 of MZE001 in healthy volunteers. ClinicalTrials.gov Identifier: NCT05249621. Accessed February 27 2025. https:\/\/clinicaltrials.gov\/study\/NCT05249621"},{"key":"e_1_3_3_90_2","unstructured":"Wantuch S. Hematopoietic Stem Cell Gene Therapy for Pompe Disease Using a Novel Recombinant Form of Acid-Alpha Glucosidase. UCL Discovery; 2023. Accessed February 27 2025. https:\/\/discovery.ucl.ac.uk\/id\/eprint\/10167394\/"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2022.10.017"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00325"},{"key":"e_1_3_3_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2012.44"},{"key":"e_1_3_3_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2014.10.068"},{"key":"e_1_3_3_95_2","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.13740"},{"key":"e_1_3_3_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.08.003"},{"key":"e_1_3_3_97_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.57"},{"key":"e_1_3_3_98_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0806809"},{"key":"e_1_3_3_99_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.03.002"},{"key":"e_1_3_3_100_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.11.046"},{"key":"e_1_3_3_101_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1336599"},{"key":"e_1_3_3_102_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01929"},{"key":"e_1_3_3_103_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.07.004"},{"key":"e_1_3_3_104_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-01038-0"},{"key":"e_1_3_3_105_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.04.15"},{"key":"e_1_3_3_106_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26237223"},{"key":"e_1_3_3_107_2","doi-asserted-by":"publisher","DOI":"10.3390\/diseases4040033"}],"container-title":["Clinical Medicine Insights: Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/11795565251337900","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/11795565251337900","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/11795565251337900","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T11:53:09Z","timestamp":1754913189000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/11795565251337900"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":106,"alternative-id":["10.1177\/11795565251337900"],"URL":"https:\/\/doi.org\/10.1177\/11795565251337900","relation":{},"ISSN":["1179-5565","1179-5565"],"issn-type":[{"value":"1179-5565","type":"print"},{"value":"1179-5565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"article-number":"11795565251337900"}}