{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:29:00Z","timestamp":1790152140627,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,4,9]],"date-time":"2014-04-09T00:00:00Z","timestamp":1397001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Enzyme\u2010replacement therapy (ERT) in Pompe disease\u2014an inherited metabolic disorder caused by acid \u03b1\u2010glucosidase deficiency and characterized in infants by generalized muscle weakness and cardiomyopathy\u2014can be complicated by immune responses. Infants that do not produce any endogenous acid \u03b1\u2010glucosidase, so\u2010called CRIM\u2010negative patients, reportedly develop a strong response. We report the clinical outcome of our Dutch infants in relation to their CRIM status and immune response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eleven patients were genotyped and their CRIM status was determined. Antibody formation and clinical outcome were assessed for a minimum of 4 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ERT was commenced between 0.1 and 8.3 months of age, and patients were treated from 0.3 to 13.7 years. All patients developed antibodies. Those with a high antibody titer (above 1:31,250) had a poor response. The antibody titers varied substantially between patients and did not strictly correlate with the patients\u2019 CRIM status. Patients who started ERT beyond 2 months of age tended to develop higher titers than those who started earlier. All three CRIM\u2010negative patients in our study succumbed by the age of 4 years seemingly unrelated to the height of their antibody titer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Antibody formation is a common response to ERT in classic infantile Pompe disease and counteracts the effect of treatment. The counteracting effect seems determined by the antibody:enzyme molecular stoichiometry. The immune response may be minimized by early start of ERT and by immune modulation, as proposed by colleagues. The CRIM\u2010negative status itself seems associated with poor outcome.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10545-014-9707-6","type":"journal-article","created":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T19:49:05Z","timestamp":1396986545000},"page":"305-314","source":"Crossref","is-referenced-by-count":88,"title":["Enzyme therapy and immune response in relation to CRIM status: the Dutch experience in classic infantile Pompe disease"],"prefix":"10.1002","volume":"38","author":[{"given":"Carin M.","family":"van Gelder","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Hoogeveen\u2010Westerveld","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases Erasmus MC University Medical Center Dr Molewaterplein 50 Rotterdam 3015 GE The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian A.","family":"Kroos","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases Erasmus MC University Medical Center Dr Molewaterplein 50 Rotterdam 3015 GE The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Plug","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ans T.","family":"van der Ploeg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold J. 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