{"doi":"10.1007/s10545-005-4415-x","title":"Monitoring enzyme replacement therapy in Fabry disease—Role of urine globotriaosylceramide","abstract":"<jats:title>Summary</jats:title><jats:p>Anderson‐Fabry disease (referred to as Fabry disease) is an X‐linked disorder characterized by a deficiency of the lysosomal enzyme <jats:italic>α</jats:italic>‐galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb<jats:sub>3</jats:sub>), the main substrate of the defective enzyme. Enzyme replacement therapy (ERT) offers a specific treatment for patients with Fabry disease, though monitoring of treatment is hampered by a lack of surrogate markers of response. In this study, the efficacy of long‐term ERT in six Fabry hemizygotes and two symptomatic heterozygotes has been evaluated. Patients were administered recombinant <jats:italic>α</jats:italic>‐galactosidase A every 2 weeks for up to a year. The efficacy of ERT was assessed by monitoring symptomatology and renal function. Urinary glycolipid concentration was estimated by a novel tandem mass spectrometric method. Urine glycolipid (Gb<jats:sub>3</jats:sub>) was elevated at baseline and fell impressively on ERT where patients were hemizygotes and in the absence of renal transplantation. In heterozygotes and in a recipient of a renal allograft, elevations and changes in urine glycolipids were less pronounced. In one patient, after several months of ERT, there was a transient increase in Gb<jats:sub>3</jats:sub> concentrations to baseline (pre‐ERT) levels, associated with the presence of antibodies to the recombinant <jats:italic>α</jats:italic>‐galactosidase A. The marked decline in urine Gb<jats:sub>3</jats:sub> on ERT, and its subsequent increase in association with an inhibitory antibody response, suggest that this analyte deserves further investigation as a potential marker of disease severity and response to treatment.</jats:p>","journal":"Journal of Inherited Metabolic Disease","year":2005,"id":14456,"datarank":6.192796333721811,"base_score":4.51085950651685,"endowment":4.51085950651685,"self_citation_contribution":0.6766289259775276,"citation_network_contribution":5.516167407744283,"self_endowment_contribution":0.6766289259775276,"citer_contribution":5.516167407744283,"corpus_percentile":null,"corpus_rank":null,"citation_count":90,"citer_count":88,"citers_with_citation_signal":79,"citers_with_endowment":79,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":114100,"name":"J. Calvin","orcid":null,"position":1,"is_corresponding":false},{"id":114101,"name":"S. Hogg","orcid":null,"position":2,"is_corresponding":false},{"id":114102,"name":"E. O'Driscoll","orcid":null,"position":3,"is_corresponding":false},{"id":114103,"name":"D. Halsall","orcid":null,"position":4,"is_corresponding":false},{"id":114104,"name":"K. Burling","orcid":null,"position":5,"is_corresponding":false},{"id":114105,"name":"G. Maguire","orcid":null,"position":6,"is_corresponding":false},{"id":114106,"name":"N. Wright","orcid":null,"position":7,"is_corresponding":false},{"id":114107,"name":"T. M. Cox","orcid":null,"position":8,"is_corresponding":false},{"id":114108,"name":"P. J. Meikle","orcid":null,"position":9,"is_corresponding":false},{"id":114109,"name":"P. B. Deegan","orcid":null,"position":10,"is_corresponding":false},{"id":114099,"name":"P. D. Whitfield","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.51085950651685,"endowment":4.51085950651685,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15702403","pmcid":null,"openalex_id":"https://openalex.org/W2026923881","authors":[],"funders":[],"total_grants":0,"fwci":4.4605,"citation_percentile":0.9484819,"influential_citations":0,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":2},{"year":2014,"count":3},{"year":2015,"count":4},{"year":2016,"count":3},{"year":2017,"count":1},{"year":2018,"count":4},{"year":2019,"count":3},{"year":2020,"count":2},{"year":2021,"count":3},{"year":2022,"count":4},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1007/s10545-005-4415-x","host_type":"publisher"},{"url":"https://doi.org/10.1007/s10545-005-4415-x","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15702403","host_type":"repository"},{"url":"http://hdl.handle.net/2440/17331","host_type":"repository"}],"fields_of_study":["Lysosomal Storage Disorders Research","Trypanosoma species research and implications","Biomedical Research and Pathophysiology","Medicine","Adult","Biomarkers","DNA Mutational Analysis","Fabry Disease","Female","Glycolipids","Heterozygote","Humans","Immunoassay","Isoenzymes","Kidney Transplantation","Male","Mass Spectrometry","Middle Aged","Models, Chemical","Pain","Recombinant Proteins","Spectrometry, Mass, Electrospray Ionization","Surveys and Questionnaires","Time Factors","Trihexosylceramides","alpha-Galactosidase"],"mesh_terms":["Adult","alpha-Galactosidase","Fabry Disease","DNA Mutational Analysis","Female","Glycolipids","Heterozygote","Humans","Immunoassay","Isoenzymes","Male","Middle Aged","Models, Chemical","Pain","Surveys and Questionnaires","Recombinant Proteins","Mass Spectrometry","Time Factors","Trihexosylceramides","Biomarkers","Kidney Transplantation","Spectrometry, Mass, Electrospray Ionization"],"keywords":["Globotriaosylceramide","Enzyme replacement therapy","Fabry disease","Alpha-galactosidase","Medicine","Urine","Internal medicine","Urinary system","Urology","Renal function","Transplantation","Gastroenterology","Endocrinology","Disease"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T10:13:57.361814Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}