{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:04:45Z","timestamp":1793505885618,"version":"4.5.0"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":57,"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>Pompe disease is a rare, progressive lysosomal storage disorder caused by acid \u03b1-glucosidase deficiency, leading to glycogen accumulation, proximal muscle weakness, and respiratory decline. Enzyme replacement therapy (ERT) significantly improves survival and stabilizes motor function, but IgE-mediated hypersensitivity reactions (HSRs) can critically compromise treatment, posing a major clinical challenge. Desensitization protocols allow temporary tolerance to ERT, yet breakthrough reactions may occur, necessitating adjunctive strategies such as omalizumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We report a 40-year-old woman with late-onset Pompe disease who developed severe IgE-mediated HSRs to alglucosidase alfa after years of uneventful therapy. Basophil activation testing (BAT) and serum-specific IgE confirmed an IgE-mediated mechanism. A 15-step, 5-bag desensitization protocol allowed temporary tolerance, but breakthrough reactions required therapy interruption. Upon switching to avalglucosidase alfa, BAT demonstrated IgE cross-reactivity, and a new desensitization protocol was implemented. Initial infusions were complicated by recurrent HSRs. The addition of subcutaneous omalizumab (300\u00a0mg monthly), administered two days before ERT, enabled safe reintroduction. Moreover, therapy was resumed gradually, starting at 50% of the target dose and escalating stepwise to the full therapeutic dose, resulting in uninterrupted treatment. Follow-up showed stable neuromuscular and respiratory function, progressive decline in BAT reactivity, and improved quality of life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This case highlights the critical role of BAT in diagnosing and monitoring IgE-mediated HSRs, the efficacy of individualized desensitization protocols, and the utility of omalizumab as an adjunctive therapy in refractory cases. In rare diseases like Pompe, documenting such integrated allergological strategies provides practical guidance for maintaining access to life-prolonging therapy and offers a reproducible framework for managing complex allergic complications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-026-04385-4","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T11:44:52Z","timestamp":1778759092000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Combined omalizumab and desensitization to control IgE-mediated hypersensitivity in enzyme replacement therapy for late-onset Pompe disease"],"prefix":"10.1186","volume":"21","author":[{"given":"Alberto","family":"Lerario","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Abati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Sciacco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo Pietro","family":"Comi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1942-2601","authenticated-orcid":false,"given":"Vanessa","family":"Desantis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"D\u2019Amore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Giovanni","family":"Solimando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Ria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Corti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8373-0532","authenticated-orcid":false,"given":"Federico","family":"Spataro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"4385_CR1","doi-asserted-by":"publisher","unstructured":"Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med. 2006;8:267\u2013288. https:\/\/doi.org\/10.1097\/01.gim.0000218152.87434.f3.","DOI":"10.1097\/01.gim.0000218152.87434.f3"},{"key":"4385_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 AJJ. Pompe\u2019s disease. Lancet. 2008;372:1342\u201353. https:\/\/doi.org\/10.1016\/S0140-6736(08)61555-X.","journal-title":"Lancet"},{"key":"4385_CR3","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. https:\/\/doi.org\/10.1016\/S1474-4422(21)00241-6.","journal-title":"Lancet Neurol"},{"key":"4385_CR4","doi-asserted-by":"publisher","unstructured":"Lessard LER, Tard C, Salort-Campana E, et al. Hypersensitivity infusion-associated reactions induced by enzyme replacement therapy in a cohort of patients with late-onset Pompe disease: an experience from the French Pompe Registry. Mol Genet Metab. 2023;139:107611. https:\/\/doi.org\/10.1016\/j.ymgme.2023.107611.","DOI":"10.1016\/j.ymgme.2023.107611"},{"key":"4385_CR5","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.jaci.2008.02.044","volume":"122","author":"MC Castells","year":"2008","unstructured":"Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI, et al. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. 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Basophil Activation Test: Bridging Allergy and Oncology for Diagnostic, Therapeutic and Prognostic Applications in AllergoOncology: An EAACI Position Paper. Allergy. 2025;80(8):2097\u2013112.","journal-title":"Allergy"},{"key":"4385_CR10","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1111\/all.15957","volume":"79","author":"C Mayorga","year":"2024","unstructured":"Mayorga C, \u00c7elik GE, Pascal M, et al. Flow-based basophil activation test in immediate drug hypersensitivity. An EAACI task force position paper. Allergy. 2024;79:580\u2013600.","journal-title":"Allergy"},{"key":"4385_CR11","doi-asserted-by":"publisher","first-page":"101207","DOI":"10.1016\/j.ymgmr.2025.101207","volume":"43","author":"M Gendive","year":"2025","unstructured":"Gendive M, Delgado TC, Unceta M, et al. Successful desensitization protocol to alglucosidase and avalglucosidase alfa in a patient with infantile-onset Pompe disease. 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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. Genet Med. 2023;25:100328. https:\/\/doi.org\/10.1016\/j.gim.2022.10.010.","journal-title":"Genet Med"},{"key":"4385_CR14","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1111\/all.12886","volume":"71","author":"C Mayorga","year":"2016","unstructured":"Mayorga C, Celik G, Rouzaire P, et al. In vitro tests for drug hypersensitivity reactions: an ENDA\/EAACI Drug Allergy Interest Group position paper. Allergy. 2016;71:1103\u201334. https:\/\/doi.org\/10.1111\/all.12886.","journal-title":"Allergy"},{"key":"4385_CR15","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1186\/s13023-024-03516-z","volume":"27","author":"F Spataro","year":"2024","unstructured":"Spataro F, Ria R, Chaoul N, Solimando AG, Desantis V, Vacca A, et al. 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The work was carried out in compliance with the Declaration of Helsinki. This study was approved by the Local Ethics Committee IRCCS Istituto Oncologico \u201cGabriella Serio\u201d of Bari, Italy, with protocol number 2461.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Authors declare no conflicts of interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"244"}}