{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T22:52:26Z","timestamp":1772059946394,"version":"3.50.1"},"reference-count":41,"publisher":"Walter de Gruyter GmbH","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2019-0163_s_999_w2aab3b7b4b1b6b1aab1c17b1Aa\">\n                  <jats:title id=\"d679415e16740_w2aab3b7b4b1b6b1aab1c17b1aAa\">Background<\/jats:title>\n                  <jats:p>Alkaptonuria (OMIM: 203500) is an inborn error of metabolism due to homogentisate 1,2-dioxygenase homogentisic acid 1,2 dioxygenase (HGD) enzyme deficiency. Due to the enzyme deficiency, homogentisic acid cannot be converted to maleylacetoacetate and it accumulates in body fluids. Increased homogentisic acid is converted to benzoquinones, the resulting benzoquinones are converted to melanin-like pigments, and these pigments are deposited in collagen \u2013 this process is called ochronosis. In patients with alkaptonuria, the urine is darkened, which is misinterpreted as hematuria, the incidences of renal stones, arthritis and cardiac valve calcification are increased, and spontaneous tendon ruptures, prostatitis and prostate stones can be encountered. The present study aimed to evaluate the <jats:italic>HGD<\/jats:italic> gene mutations in 14 patients with alkaptonuria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2019-0163_s_998_w2aab3b7b4b1b6b1aab1c17b2Aa\">\n                  <jats:title id=\"d679415e16751_w2aab3b7b4b1b6b1aab1c17b2aAa\">Methods<\/jats:title>\n                  <jats:p>Fourteen patients diagnosed with alkaptonuria and followed up from 1990 to 2014 were retrospectively evaluated. Their demographic, clinical and treatment-related data were retrieved from hospital files. For mutation analysis, genomic DNAs of the patients were isolated from their peripheral blood samples. Variations in the <jats:italic>HGD<\/jats:italic> gene were scanned on the HGD-mutation database (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/hgddatabase.cvtisr.sk\">http:\/\/hgddatabase.cvtisr.sk<\/jats:ext-link>).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2019-0163_s_997_w2aab3b7b4b1b6b1aab1c17b3Aa\">\n                  <jats:title id=\"d679415e16765_w2aab3b7b4b1b6b1aab1c17b3aAa\">Results<\/jats:title>\n                  <jats:p>Among 14 patients, the female\/male ratio was 1\/1 and the median age was 9 years (range, 6\u201359 years). All patients were symptomatic at their first visit and the most common symptom was dark urine (71%) followed by arthralgia. Independent of the urinary homogentisic acid concentrations, patients with the presenting symptom of arthralgia were elder. Nine different mutations including p.Ser59AlafsX52, p.Gly161Arg, p.Asn219Ser, p.Gly251Asp, p.Pro274Leu, p.Arg330Ser, p.Gly372Ala, c.656_657insAATCAA and a novel mutation of p.Val316Ile were detected. All of the pediatric-age patients (n\u2009=\u200913) were treated with ascorbic acid at a dose of 250\u20131000 mg\/day.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2019-0163_s_996_w2aab3b7b4b1b6b1aab1c17b4Aa\">\n                  <jats:title id=\"d679415e16773_w2aab3b7b4b1b6b1aab1c17b4aAa\">Conclusions<\/jats:title>\n                  <jats:p>Nine different <jats:italic>HGD<\/jats:italic> gene mutations with a novel one, p.Val316Ile, were detected. The most common mutation was p.Ser59AlafsX52 for the <jats:italic>HGD<\/jats:italic> gene followed by p.Gly161Arg and p.asn219Ser, which can be considered specific to the Turkish population.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2019-0163","type":"journal-article","created":{"date-parts":[[2020,1,12]],"date-time":"2020-01-12T09:12:56Z","timestamp":1578820376000},"page":"289-294","source":"Crossref","is-referenced-by-count":10,"title":["Presentation of 14 alkaptonuria patients from Turkey"],"prefix":"10.1515","volume":"33","author":[{"given":"Alper Ilker","family":"Akbaba","sequence":"first","affiliation":[{"name":"Department of Pediatrics , Hacettepe University Faculty of Medicine , Gevher Nesibe Cd., Alt\u0131nda\u011f, 06230 , Ankara , Turkey , Phone: +90 505 329 4554"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u0131za K\u00f6ksal","family":"Ozg\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolism, Institute of Child Health , Hacettepe University , Ankara , Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Dursun","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolism , Hacettepe University Faculty of Medicine , Ankara , Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2020,1,13]]},"reference":[{"key":"2023040101034631532_j_jpem-2019-0163_ref_001_w2aab3b7b4b1b6b1ab1b6b1Aa","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Ca\u00f1\u00f3n JM, Granadino B, Beltr\u00e1n-Valero de Bernab\u00e9 D, Renedo M, Fern\u00e1ndez-Ruiz E, et al. The molecular basis of alkaptonuria. Nature Genet 1996;14:19\u201324.","DOI":"10.1038\/ng0996-19"},{"key":"2023040101034631532_j_jpem-2019-0163_ref_002_w2aab3b7b4b1b6b1ab1b6b2Aa","doi-asserted-by":"crossref","unstructured":"Phornphutkul C, Introne WJ, Perry MB, Bernardini I, Murphey MD, et al. Natural history of alkaptonuria. New Eng J Med 2002;347:2111\u201321.","DOI":"10.1056\/NEJMoa021736"},{"key":"2023040101034631532_j_jpem-2019-0163_ref_003_w2aab3b7b4b1b6b1ab1b6b3Aa","unstructured":"Milch RA. Studies of alkaptonuria: inheritance of 47 cases in eight highly inter-related Dominican kindreds. Am J Hum Genet 1960;12:76\u201385."},{"key":"2023040101034631532_j_jpem-2019-0163_ref_004_w2aab3b7b4b1b6b1ab1b6b4Aa","doi-asserted-by":"crossref","unstructured":"Cervenansky J, Sitaj S, Urbanek T. Alkaptonuria and ochronosis. 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