{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:17:43Z","timestamp":1782814663914,"version":"3.54.5"},"reference-count":24,"publisher":"BMJ","issue":"12","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2021,11,2]]},"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:p>Alkaptonuria (AKU) is a rare autosomal recessive disorder with a global incidence of 1 in 250\u2009000 to 1\u2009million people worldwide. It results from a deficiency of the enzyme homogentisic acid (HGA) oxidase which when absent, leads to an accumulation of HGA. Without this enzymatic degradation, HGA deposits in connective tissues resulting in pigmentation (ochronosis), plaque formation and accelerated cartilage destruction. With this, many patients who suffer from AKU develop ochronotic arthropathies, tendon ruptures, fractures, and chronic joint pain. Similarly, patients can develop cardiac valvular dysfunction and interstitial renal disease. Our two cases highlight the array of pathologies seen in AKU and, in light of newly published research, give us a platform from which we can discuss the developments in management of this rare disease.<\/jats:p>","DOI":"10.1136\/bcr-2021-244240","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T11:22:53Z","timestamp":1638876173000},"page":"e244240","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Alkaptonuria: clinical manifestations and an updated approach to treatment of a rare disease"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8088-7016","authenticated-orcid":false,"given":"Ryan Curtis","family":"Roopnarinesingh","sequence":"first","affiliation":[{"name":"Department of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel Edward","family":"Donlon","sequence":"additional","affiliation":[{"name":"Department of Upper GI Surgery, St.James Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John V","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Upper GI Surgery, St.James Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,12,7]]},"reference":[{"key":"2025082701575871000_14.12.e244240.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021736"},{"key":"2025082701575871000_14.12.e244240.2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(63)90089-5"},{"key":"2025082701575871000_14.12.e244240.3","first-page":"73","article-title":"The Croonian lectures on inborn errors of metabolism. Lecture II. alkaptonuria","volume":"2","author":"ArchibaldE","year":"1908","journal-title":"Lancet"},{"key":"2025082701575871000_14.12.e244240.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)41972-6"},{"key":"2025082701575871000_14.12.e244240.5","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1177\/0004563217691065","article-title":"The effect of nitisinone on homogentisic acid and tyrosine: a two-year survey of patients attending the National alkaptonuria centre, Liverpool","volume":"54","author":"Milan","year":"2017","journal-title":"Ann Clin Biochem"},{"key":"2025082701575871000_14.12.e244240.6","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9363-z"},{"key":"2025082701575871000_14.12.e244240.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.04.016"},{"key":"2025082701575871000_14.12.e244240.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2004.12.017"},{"key":"2025082701575871000_14.12.e244240.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2016.01.010"},{"key":"2025082701575871000_14.12.e244240.10","doi-asserted-by":"crossref","DOI":"10.4161\/rdis.27475","article-title":"Alkaptonuria","volume":"1","author":"Mistry","year":"2013","journal-title":"Rare Diseases"},{"key":"2025082701575871000_14.12.e244240.11","doi-asserted-by":"publisher","DOI":"10.3121\/cmr.2.4.209"},{"key":"2025082701575871000_14.12.e244240.12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/BF02208354","article-title":"Spinal abnormalities similar to ankylosing spondylitis in a 58-year-old woman with ochronosis","volume":"14","author":"Kabasakal","year":"1995","journal-title":"Clin Rheumatol"},{"key":"2025082701575871000_14.12.e244240.13","doi-asserted-by":"crossref","first-page":"080310185205909","DOI":"10.1111\/j.1365-2559.2008.03000.x","article-title":"Alkaptonuria--a review of surgical and autopsy pathology","volume":"53","author":"Helliwell","year":"2008","journal-title":"Histopathology"},{"key":"2025082701575871000_14.12.e244240.14","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq246"},{"key":"2025082701575871000_14.12.e244240.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2018.07.011"},{"key":"2025082701575871000_14.12.e244240.16","first-page":"464","article-title":"Alkaptonuria and renal failure: a case report and review of the literature","volume":"5","author":"Venkataseshan","year":"1992","journal-title":"Mod Pathol"},{"key":"2025082701575871000_14.12.e244240.17","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.ymgme.2021.05.007","article-title":"Evaluating the aortic stenosis phenotype before and after the effect of homogentisic acid lowering therapy: analysis of a large cohort of eighty-one alkaptonuria patients","volume":"133","author":"Ranganath","year":"2021","journal-title":"Mol Genet Metab"},{"key":"2025082701575871000_14.12.e244240.18","doi-asserted-by":"crossref","DOI":"10.1186\/s13023-020-01611-5","article-title":"Bone fragility in patients affected by congenital diseases non skeletal in origin","volume":"16","author":"Masi","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"2025082701575871000_14.12.e244240.19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.2003.01145.x"},{"key":"2025082701575871000_14.12.e244240.20","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.11.3930"},{"key":"2025082701575871000_14.12.e244240.21","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1007\/s10545-015-9844-6","article-title":"Old treatments for new insights and strategies: proposed management in adults and children with alkaptonuria","volume":"38","author":"Arnoux","year":"2015","journal-title":"J Inherit Metab Dis"},{"key":"2025082701575871000_14.12.e244240.22","first-page":"71","article-title":"A patient survey on the impact of alkaptonuria symptoms as perceived by the patients and their experiences of receiving diagnosis and care","volume":"53","author":"Rudebeck","year":"2020","journal-title":"JIMD Rep"},{"key":"2025082701575871000_14.12.e244240.23","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206033"},{"key":"2025082701575871000_14.12.e244240.24","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/S2213-8587(20)30228-X","article-title":"Efficacy and safety of once-daily nitisinone for patients with alkaptonuria (SONIA 2): an international, multicentre, open-label, randomised controlled trial","volume":"8","author":"Ranganath","year":"2020","journal-title":"Lancet Diabetes Endocrinol"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2021-244240","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T08:58:10Z","timestamp":1756285090000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2021-244240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":24,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12,7]]},"published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1136\/bcr-2021-244240"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2021-244240","relation":{},"ISSN":["1757-790X"],"issn-type":[{"value":"1757-790X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]}}}