{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T15:28:37Z","timestamp":1788190117363,"version":"build-2803163510"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"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>Classical homocystinuria (HCU) is a rare genetic metabolic disorder resulting in elevated homocysteine and methionine levels. The clinical characteristics and associated complications of HCU are well documented. However, there is limited published research on the clinical burden of patients with HCU, especially stratified by total homocysteine (tHcy) levels. This study aimed to describe the overall clinical burden of patients with HCU in the United States and key clinical events by tHcy levels using administrative claims data.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This non-interventional retrospective cohort analysis from January 01, 2016, through September 30, 2021, used Optum\u2019s de-identified Market Clarity Data. Patients who had 1 or more International Classification of Diseases, Tenth Revision code for homocystinuria (E72.11) or the signs, disease, and symptoms term <jats:italic>homocystinuria<\/jats:italic> in the natural language processing dataset were included. To obtain a study population most likely to have HCU, stratifications by tHcy levels, clinical characteristics, and phenotypic expressions were applied to refine the cohort. Included patients were then stratified by highest tHcy level. Clinical burden was measured by category of HCU-related events. Descriptive statistics were reported.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Six hundred thirty-three patients met the inclusion criteria, and 601 patients had a tHcy level:\u2009&lt;\u200950\u00a0\u00b5M (n\u2009=\u2009278), 50 to\u2009&lt;\u2009100\u00a0\u00b5M (n\u2009=\u2009212), and\u2009\u2265\u2009100\u00a0\u00b5M (n\u2009=\u2009111). Among the 601 patients with a tHcy level, almost one-half (n\u2009=\u2009297, 49.4%) had at least one thrombotic\/thromboembolic, skeletal, ocular, or neurological event and 14.1% (n\u2009=\u200985) had multiple events. Thrombotic\/thromboembolic events (n\u2009=\u2009186, 30.9%) were the most common type of events, followed by skeletal (n\u2009=\u2009100, 16.6%), ocular (n\u2009=\u200963, 10.5%), and neurological events (n\u2009=\u200950, 8.3%). During follow-up, 5.7% (n\u2009=\u200934) of the patients died. All events assessed were more prevalent in the 50 to\u2009&lt;\u2009100\u00a0\u00b5M group and\u2009\u2265\u2009100\u00a0\u00b5M group compared with those in the\u2009&lt;\u200950\u00a0\u00b5M group.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>As has been believed, patients with tHcy\u2009\u2265\u2009100\u00a0\u00b5M carried a substantial clinical burden, but the burden is also very high in those whose levels were\u2009\u2265\u200950\u00a0\u00b5M. Thrombotic\/thromboembolic events were more common than skeletal, ocular, or neurological events. Meaningfully lowered tHcy levels may help to reduce significant clinical events.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-025-03530-9","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T14:01:55Z","timestamp":1737727315000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["High clinical burden of classical homocystinuria in the United States: a retrospective analysis"],"prefix":"10.1186","volume":"20","author":[{"given":"Mahim","family":"Jain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehul","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamlesh M.","family":"Thakker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Rava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Pelts Block","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette","family":"Ndiba-Markey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"issue":"1","key":"3530_CR1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s10545-016-9979-0","volume":"40","author":"AA Morris","year":"2017","unstructured":"Morris AA, Ko\u017eich V, Santra S, Andria G, Ben-Omran TI, Chakrapani AB, et al. 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No direct identifiers of individuals, employers, households, or providers are included. Since Optum data is de-identified and its use does not require IRB approval, it typically does not require patient consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MJ has received consultancy fees from Travere Therapeutics, Inc. MS is an employee and stock\/options holder (vested and unvested) of Travere Therapeutics, Inc. KMT is an employee of Notting Hill Consulting LLC which has received consulting fees from Travere Therapeutics, Inc. AR is an employee of Genesis Research Group, which receives consulting fees from Travere Therapeutics, Inc. for this study and other related studies. APB is an employee and stockholder of Travere Therapeutics Inc. CNM was an employee of Genesis Research Group at the time of the study, which receives consulting fees from Travere Therapeutics, Inc. for this study and other related studies. LP is a former employee and stock\/options holder (vested and unvested) of Travere Therapeutics, Inc.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"37"}}