{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T14:16:10Z","timestamp":1791728170437,"version":"4.3.4"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Orphan Technologies","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Health Serv Res"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Classical homocystinuria (HCU), an inborn error of homocysteine metabolism, has previously been estimated to affect approximately 1 in 100,000\u2013200,000 people in the United States (US). HCU is poorly detected by newborn screening, resulting in underestimates of its prevalence. This study compared characteristics, healthcare use and costs, and projected prevalence between patients with diagnosed HCU, elevated total homocysteine (tHcy), and diagnosed phenylketonuria (PKU).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Patients in the MarketScan\u00ae Research Databases were identified with strictly-defined HCU (&gt;\u20092 diagnoses, including 1 ICD-10), broadly-defined HCU (&gt;\u20091 ICD-10), elevated tHcy (&gt;\u200920\u2009\u03bcmol\/L) without an HCU diagnosis, or\u2009&gt;\u20091 ICD-9\/ICD-10 PKU diagnosis during 1\/1\/2010\u201312\/31\/2016 (first qualifying claim\u2009=\u2009index). Demographics and healthcare utilization and costs per patient per month (PPPM) were compared between all cohorts, frequencies of comorbidities and medications were compared between HCU and elevated tHcy patients, and healthcare provider types were assessed among HCU patients. The prevalence of patients meeting each cohort definition was projected to the United States (US) population.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Patients with strictly-defined (<jats:italic>N<\/jats:italic>\u2009=\u20092450) and broadly-defined (<jats:italic>N<\/jats:italic>\u2009=\u20096613) HCU, and with elevated tHcy (<jats:italic>N<\/jats:italic>\u2009=\u20092017), were significantly older than PKU patients (<jats:italic>N<\/jats:italic>\u2009=\u20095120) (57 vs. 56 vs. 53 vs. 18\u2009years; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Vitamin D deficiency, hyperlipidemia, folic acid\/B vitamins, and lipid-lowering medications, among others, were more common among diagnosed HCU patients vs. those with elevated tHcy (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Rates of healthcare utilization were generally higher among HCU and elevated tHcy patients, compared to PKU, though total healthcare costs were similar between groups. Most HCU patients (~\u200938%) received their index diagnosis from a primary care physician; very few (~\u20091%) had any claim from a geneticist during their enrollment. The age-adjusted national prevalence of HCU was projected at 31,162 (95% CI: 30,411 \u2013 31,913; ~\u20091 in 10,000 of the US population) using the broad definition.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The actual prevalence of HCU may be <jats:underline>&gt;<\/jats:underline>\u200910 times prior estimates, at 1 in 10,000 in the US, and this study suggests that HCU is not being diagnosed until later in life. Improvements to newborn screening, detection in young children, and physician education regarding HCU among patients may be necessary to alleviate the burden of this genetic disease.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12913-020-5054-5","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T05:03:49Z","timestamp":1583471029000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Prevalence, characteristics, and costs of diagnosed homocystinuria, elevated homocysteine, and phenylketonuria in the United States: a retrospective claims-based comparison"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-2215","authenticated-orcid":false,"given":"Marcia","family":"Sellos-Moura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Glavin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lapidus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn R.","family":"Lew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra E.","family":"Irwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,6]]},"reference":[{"issue":"3613","key":"5054_CR1","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1126\/science.143.3613.1443","volume":"143","author":"SH Mudd","year":"1964","unstructured":"Mudd SH, Finkelstein JD, Irreverre F, Laster L. Homocystinuria: an enzymatic defect. Science. 1964;143(3613):1443\u20135.","journal-title":"Science."},{"issue":"4","key":"5054_CR2","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/0026-0495(74)90057-2","volume":"23","author":"JD Finkelstein","year":"1974","unstructured":"Finkelstein JD. Methionine metabolism in mammals: the biochemical basis for homocystinuria. Metabolism. 1974;23(4):387\u201398.","journal-title":"Metabolism."},{"issue":"9","key":"5054_CR3","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1001\/jama.1965.03090090017003","volume":"193","author":"RN Schimke","year":"1965","unstructured":"Schimke RN, McKusick VA, Huang T, Pollack AD. Homocystinuria: studies of 20 families with 38 affected members. JAMA. 1965;193(9):711\u20139.","journal-title":"JAMA."},{"key":"5054_CR4","unstructured":"US National Library of Medicine: Homocystinuria. In: Genetics Home Reference. 2016. https:\/\/ghr.nlm.nih.gov\/condition\/homocystinuria#sourcesforpage. Accessed 15 Oct 2019."},{"key":"5054_CR5","unstructured":"Mandava P. Homocystinuria\/Homocysteinemia. In: Drugs and Diseases. Medscape. 2018. https:\/\/emedicine.medscape.com\/article\/1952251-overview#showall. Accessed 15 Oct 2019."},{"issue":"1","key":"5054_CR6","first-page":"1","volume":"37","author":"SH Mudd","year":"1985","unstructured":"Mudd SH, Skovby F, Levy HL, et al. The natural history of homocystinuria due to cystathionine \u03b2-synthase deficiency. Am J Hum Genet. 1985;37(1):1\u201331.","journal-title":"Am J Hum Genet"},{"issue":"3","key":"5054_CR7","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.jpeds.2008.09.015","volume":"154","author":"M Jano\u0161\u00edk","year":"2009","unstructured":"Jano\u0161\u00edk M, Sokolov\u00e1 J, Jano\u0161\u00edkov\u00e1 B, Krijt J, Klatovsk\u00e1 V, Ko\u017eich V. Birth prevalence of homocystinuria in Central Europe: frequency and pathogenicity of mutation c. 1105C> T (p. R369C) in the cystathionine beta-synthase gene. J Pediatr. 2009;154(3):431\u20137.","journal-title":"J Pediatr"},{"issue":"6","key":"5054_CR8","first-page":"830","volume":"144","author":"H Refsum","year":"2004","unstructured":"Refsum H, Fredriksen \u00c5, Meyer K, Ueland PM, Kase BF. Birth prevalence of homocystinuria. J Pediatr. 2004;144(6):830\u20132.","journal-title":"J Pediatr"},{"key":"5054_CR9","doi-asserted-by":"publisher","first-page":"CD008840","DOI":"10.1002\/14651858.CD008840.pub4","volume":"10","author":"J Walter","year":"2015","unstructured":"Walter J, Jahnke N, Remmington T. Newborn screening for homocystinuria. Cochrane Database Syst Rev. 2015;10:CD008840. https:\/\/doi.org\/10.1002\/14651858.CD008840.pub4.","journal-title":"Cochrane Database Syst Rev"},{"key":"5054_CR10","unstructured":"American Factfinder. United States Census Bureau. https:\/\/factfinder.census.gov. Accessed 12 May 2018."},{"key":"5054_CR11","unstructured":"About PKU. National PKU Alliance. https:\/\/www.npkua.org\/What-is-PKU\/About-PKU. Accessed 15 Oct 2019."},{"issue":"1","key":"5054_CR12","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s10545-016-9979-0","volume":"40","author":"AM Morris","year":"2017","unstructured":"Morris AM, Kozich V, Santra S, et al. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis. 2017;40(1):49\u201374.","journal-title":"J Inherit Metab Dis"}],"container-title":["BMC Health Services Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12913-020-5054-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12913-020-5054-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12913-020-5054-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,6]],"date-time":"2021-03-06T00:54:43Z","timestamp":1614992083000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmchealthservres.biomedcentral.com\/articles\/10.1186\/s12913-020-5054-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,6]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["5054"],"URL":"https:\/\/doi.org\/10.1186\/s12913-020-5054-5","relation":{},"ISSN":["1472-6963"],"issn-type":[{"value":"1472-6963","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,6]]},"assertion":[{"value":"9 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All study data were accessed with protocols compliant with US patient confidentiality requirements, including the Health Insurance Portability and Accountability Act of 1996 regulations (HIPAA). As all databases used in the study are fully de-identified and compliant with the HIPPA, this study was exempted from Institutional Review Board approval and informed consent was not needed.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MS and FG are employed by Orphan Technologies. DI, KE and CL are employed by IBM Watson Health as consultants and received funding from Orphan Technologies to conduct this study. DL is a paid consultant of Orphan Technologies.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"183"}}