{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:28:42Z","timestamp":1740144522432,"version":"3.37.3"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by mutations in the gene encoding \u03b1-galactosidase A, resulting in lysosomal accumulation of globotriaosylceramide and other glycosphingolipids. Early detection of FD is challenging, accounting for delayed diagnosis and treatment initiation. This study aimed to develop an algorithm using a logistic regression model to facilitate early identification of patients based on ICD-10-GM coding using a German Sickness Fund Database.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The logistic regression model was fitted on a binary outcome variable based on either a treated FD cohort or a control cohort (without FD). Comorbidities specific to the involved organs were used as covariates to identify potential FD patients with ICD-10-GM E75.2 diagnosis but without any FD-specific medication. Specificity and sensitivity of the model were optimized to determine a likely threshold. The cut-point with the largest values for the Youden index and concordance probability method and the lowest value for closest to (0,1) was identified as 0.08 for each respective value. The sensitivity and specificity for this cut-point were 80.4% and 79.8%, respectively. Additionally, a sensitivity analysis of the potential FD patients with at least two codes of E75.2 diagnoses was performed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 284 patients were identified in the potential FD cohort using the logistic regression model. Most potential FD patients were &lt;\u200930 years old and female. The identification and incidence rates of FD in the potential FD cohort were markedly higher than those of the treated FD cohort.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This model serves as a tool to identify potential FD patients using German insurance claims data.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-024-03258-y","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T12:06:41Z","timestamp":1720526801000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling the untreated: development of a database algorithm to identify potential Fabry disease patients in Germany"],"prefix":"10.1186","volume":"19","author":[{"given":"Max J.","family":"Hilz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9707-2446","authenticated-orcid":false,"given":"Nicole","family":"Lyn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Marczykowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Werner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Pignot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elvira","family":"Ponce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Bender","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Edigkaufer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pronabesh","family":"DasMahapatra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"3258_CR1","first-page":"113","volume":"18","author":"RJ Desnick","year":"1989","unstructured":"Desnick RJ, Astrin KH, Bishop DF. Fabry disease: molecular genetics of the inherited nephropathy. Adv Nephrol Necker Hosp. 1989;18:113\u201327.","journal-title":"Adv Nephrol Necker Hosp"},{"key":"3258_CR2","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1006\/bbrc.1993.2659","volume":"197","author":"S Ishii","year":"1993","unstructured":"Ishii S, Kase R, Sakuraba H, Suzuki Y. Characterization of a mutant alpha-galactosidase gene product for the late-onset cardiac form of fabry disease. Biochem Biophys Res Commun. 1993;197:1585\u20139.","journal-title":"Biochem Biophys Res Commun"},{"key":"3258_CR3","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1750-1172-5-30","volume":"5","author":"DP Germain","year":"2010","unstructured":"Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30.","journal-title":"Orphanet J Rare Dis"},{"key":"3258_CR4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.jns.2014.06.029","volume":"344","author":"R El-Abassi","year":"2014","unstructured":"El-Abassi R, Singhal D, England JD. Fabry\u2019s disease. J Neurol Sci. 2014;344:5\u201319.","journal-title":"J Neurol Sci"},{"key":"3258_CR5","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1001\/jama.281.3.249","volume":"281","author":"PJ Meikle","year":"1999","unstructured":"Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. 1999;281:249\u201354.","journal-title":"JAMA"},{"key":"3258_CR6","unstructured":"OrphaNet. Fabry Disease [Internet]. 2012 https:\/\/www.orpha.net\/consor\/cgi-bin\/Disease_Search.php?lng=DE&data_id=94 [Accessed 28 Feb, 2023]."},{"key":"3258_CR7","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1681\/ASN.2016090964","volume":"28","author":"M Arends","year":"2017","unstructured":"Arends M, Wanner C, Hughes D, Mehta A, Oder D, Watkinson OT, et al. Characterization of classical and nonclassical fabry disease: a Multicenter Study. J Am Soc Nephrol. 2017;28:1631\u201341.","journal-title":"J Am Soc Nephrol"},{"key":"3258_CR8","doi-asserted-by":"crossref","unstructured":"Beirao I, Cabrita A, Torres M, Silva F, Aguiar P, Laranjeira F et al. Biomarkers and imaging findings of Anderson-Fabry Disease-what we know now. Diseases. 2017;5:15.","DOI":"10.3390\/diseases5020015"},{"key":"3258_CR9","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/sj.ejhg.5201184","volume":"12","author":"F Verovnik","year":"2004","unstructured":"Verovnik F, Benko D, Vujkovac B, Linthorst GE. Remarkable variability in renal disease in a large Slovenian family with fabry disease. Eur J Hum Genet. 2004;12:678\u201381.","journal-title":"Eur J Hum Genet"},{"key":"3258_CR10","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.ymgme.2007.09.013","volume":"93","author":"WR Wilcox","year":"2008","unstructured":"Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, et al. Females with fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab. 2008;93:112\u201328.","journal-title":"Mol Genet Metab"},{"key":"3258_CR11","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.2165\/11318300-000000000-00000","volume":"69","author":"RM Schaefer","year":"2009","unstructured":"Schaefer RM, Tylki-Szymanska A, Hilz MJ. Enzyme replacement therapy for fabry disease: a systematic review of available evidence. Drugs. 2009;69:2179\u2013205.","journal-title":"Drugs"},{"key":"3258_CR12","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1016\/j.clinthera.2009.09.008","volume":"31","author":"C Kampmann","year":"2009","unstructured":"Kampmann C, Linhart A, Devereux RB, Schiffmann R. Effect of agalsidase alfa replacement therapy on fabry disease-related hypertrophic cardiomyopathy: a 12- to 36-month, retrospective, blinded echocardiographic pooled analysis. Clin Ther. 2009;31:1966\u201376.","journal-title":"Clin Ther"},{"key":"3258_CR13","unstructured":"Prescribing information- Pegunigalsidase alfa [Internet]. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761161s000lbl.pdf [Accessed 4 Aug, 2023]."},{"key":"3258_CR14","unstructured":"Prescribing information-Migalastat [Internet]. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/208623lbl.pdf [Accessed 28 Feb, 2023]."},{"key":"3258_CR15","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/B978-0-444-62702-5.00017-2","volume":"132","author":"R Schiffmann","year":"2015","unstructured":"Schiffmann R. Fabry disease. Handb Clin Neurol. 2015;132:231\u201348.","journal-title":"Handb Clin Neurol"},{"key":"3258_CR16","unstructured":"InformedHealth.org [Internet]. [Internet]. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK298836\/ [Accessed 23 Jan, 2003]."},{"key":"3258_CR17","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","volume":"40","author":"ME Charlson","year":"1987","unstructured":"Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373\u201383.","journal-title":"J Chronic Dis"},{"key":"3258_CR18","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.ymgme.2018.02.014","volume":"123","author":"A Ortiz","year":"2018","unstructured":"Ortiz A, Germain DP, Desnick RJ, Politei J, Mauer M, Burlina A, et al. Fabry disease revisited: management and treatment recommendations for adult patients. Mol Genet Metab. 2018;123:416\u201327.","journal-title":"Mol Genet Metab"},{"key":"3258_CR19","doi-asserted-by":"publisher","first-page":"3762651","DOI":"10.1155\/2017\/3762651","volume":"2017","author":"I Unal","year":"2017","unstructured":"Unal I. Defining an optimal cut-point value in ROC analysis: an Alternative Approach. Comput Math Methods Med. 2017;2017:3762651.","journal-title":"Comput Math Methods Med"},{"key":"3258_CR20","unstructured":"SAS Institute Inc. 2013.SAS\/STAT\u00ae13.1 User\u2019s Guide.Cary, NC: SAS Institute Inc, chapter The LOGISTIC Procedure. [Internet]. https:\/\/support.sas.com\/documentation\/onlinedoc\/stat\/131\/logistic.pdf [Accessed 21 Dec, 2022]."},{"key":"3258_CR21","unstructured":"KM 6 statistics of the Information System of the Federal Health Monitoring. (cutoff date: 1st July 2017). [Internet]. https:\/\/statistik.arbeitsagentur.de\/DE\/Navigation\/Statistiken\/Fachstatistiken\/Beschaeftigung\/Beschaeftigung-Nav.html [Accessed 21 Dec, 2022]."},{"key":"3258_CR22","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1007\/s10545-007-0521-2","volume":"30","author":"CM Eng","year":"2007","unstructured":"Eng CM, Fletcher J, Wilcox WR, et al. Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. J Inherit Metab Dis. 2007;30:184\u201392.","journal-title":"J Inherit Metab Dis"},{"key":"3258_CR23","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1111\/j.1365-2362.2004.01309.x","volume":"34","author":"A Mehta","year":"2004","unstructured":"Mehta A, Ricci R, Widmer U, Dehout F, Garcia de Lorenzo A, Kampmann C, et al. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest. 2004;34:236\u201342.","journal-title":"Eur J Clin Invest"},{"key":"3258_CR24","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/190372a0","volume":"190","author":"MF Lyon","year":"1961","unstructured":"Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus L). Nature. 1961;190:372\u20133.","journal-title":"Nature"},{"issue":"1","key":"3258_CR25","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/cge.12613","volume":"89","author":"L Echevarria","year":"2016","unstructured":"Echevarria L, Benistan K, Toussaint A, Dubourg O, Hagege AA, Eladari D, et al. X-chromosome inactivation in female patients with fabry disease. Clin Genet. 2016;89(1):44\u201354.","journal-title":"Clin Genet"},{"issue":"1","key":"3258_CR26","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3390\/genes15010037","volume":"15","author":"R Izhar","year":"2023","unstructured":"Izhar R, Borriello M, La Russa A, Di Paola R, De A, Capasso G, et al. Fabry Disease in women: genetic basis, available biomarkers, and clinical manifestations. Genes (Basel). 2023;15(1):37.","journal-title":"Genes (Basel)"},{"key":"3258_CR27","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s004399900075","volume":"105","author":"BJ Poorthuis","year":"1999","unstructured":"Poorthuis BJ, Wevers RA, Kleijer WJ, Groener JE, de Jong JG, van Weely S, et al. The frequency of lysosomal storage diseases in the Netherlands. Hum Genet. 1999;105:151\u20136.","journal-title":"Hum Genet"},{"key":"3258_CR28","volume-title":"Fabry Disease: perspectives from 5 years of FOS","author":"M Fuller","year":"2006","unstructured":"Fuller M, Meikle PJ, Hopwood JJ. Epidemiology of lysosomal storage diseases: an overview. In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry Disease: perspectives from 5 years of FOS. Oxford: Oxford PharmaGenesis; 2006. Chapter 2."},{"key":"3258_CR29","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1002\/jmd2.12071","volume":"49","author":"AM Martins","year":"2019","unstructured":"Martins AM, Cabrera G, Molt F, Su\u00e1rez-Obando F, Vald\u00e9s RA, Varas C, et al. The clinical profiles of female patients with fabry disease in Latin America: a Fabry Registry analysis of natural history data from 169 patients based on enzyme replacement therapy status. JIMD Rep. 2019;49:107\u201317.","journal-title":"JIMD Rep"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03258-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03258-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03258-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T12:11:45Z","timestamp":1720527105000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03258-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,9]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3258"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03258-y","relation":{},"ISSN":["1750-1172"],"issn-type":[{"type":"electronic","value":"1750-1172"}],"subject":[],"published":{"date-parts":[[2024,7,9]]},"assertion":[{"value":"6 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The respective company health insurance fund (BKK) was informed about the project. All required approvals were granted. All patient level data in the database were anonymized to comply with German data protection regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Patient consent statement was not required as the records in the database were anonymized.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MJH received consultancy and speaker fees from Sanofi Genzyme and from Amicus Therapeutics, consultancy fees from Pfizer, and editor honoraria from Elsevier BV, outside of the present work. NL, EP, JB, ME, and PD are employees and may hold stock and\/or stock options in Sanofi. FM is a full-time employee of Oracle Life Sciences, Munich, Germany (formerly Cerner Enviza), which received funding from Sanofi. BW is a full-time employee of Team Gesundheit GmbH. Team Gesundheit GmbH received funding from Kantar, Health Division to perform the analyses. MP is a full-time employee of ZEG Berlin GmbH, an Oracle company. ZEG Berlin GmbH received funding from Sanofi.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"259"}}