{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:32:57Z","timestamp":1792146777219,"version":"4.4.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Hacettepe University Scientific Research and Development Office","award":["01301101001"],"award-info":[{"award-number":["01301101001"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Gastroenterol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Cystinosis is a multisystemic disease resulting from cystine accumulation primarily in kidney and many other tissues. We intended to study the evolution of less commonly seen extrarenal complications of cystinosis in a group of patients who have periods without cysteamine treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Gastrointestinal and muscular complications of cystinosis were studied in a group of 21 patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Twenty one patients were included in the study. Among them, 14 were homozygous and 3 were compound heterozygous for <jats:italic>CTNS<\/jats:italic> mutations. The median age of diagnosis was 15\u2009months (range; 5\u2009months-14\u2009years) and the mean age at last visit was 11.3\u2009\u00b1\u20096.5\u2009years. Nine patients (42%) had end stage renal disease at a mean age of 10.6\u2009years (6.5\u201317\u2009years). Abdominal ultrasonography and portal vein doppler ultrasonography were performed in19 patients, 14 of them (74%) had hepatomegaly, 10 patients (53%) had granular pattern or heterogeneity of liver. Only one patient had high transaminase levels and liver biopsy showed cystine crystals in the liver. Eleven patients (58%) had borderline or increased portal vein minimum and maximum flow velocities. One patient had CK level of 9024\u2009U\/L and electromyographic study showed active myopathic involvement. Two patients were found to have gastroesaphageal reflux only and 4 patients were found to have esophageal remnants in addition to reflux.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In addition to renal functions, extrarenal organs may be affected from cystine accumulation even in childhood, especially in patients who are incompliant to treatment, resulting in complications such as swallowing difficulty, hepatomegaly and portal hypertension.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12876-020-01385-x","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T13:05:10Z","timestamp":1596027910000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cystinosis beyond kidneys: gastrointestinal system and muscle involvement"],"prefix":"10.1186","volume":"20","author":[{"given":"Rezan","family":"Topaloglu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe","family":"G\u00fcltekingil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bora","family":"G\u00fclhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Ozaltin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00fclya","family":"Demir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00fcrkmen","family":"\u00c7iftci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Numan","family":"Demir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7a\u011fr\u0131 Mesut","family":"Temucin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysel","family":"Yuce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Okhan","family":"Akhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"1385_CR1","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1056\/NEJMra020552","volume":"3470","author":"WA Gahl","year":"2002","unstructured":"Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med. 2002;3470:111\u201321. https:\/\/doi.org\/10.1056\/NEJMra020552.","journal-title":"N Engl J Med"},{"key":"1385_CR2","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/ng0498-319","volume":"18","author":"M Town","year":"1998","unstructured":"Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet. 1998;18:319\u201324. https:\/\/doi.org\/10.1038\/ng0498-319.","journal-title":"Nat Genet"},{"key":"1385_CR3","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1093\/hmg\/ddh152","volume":"13","author":"V Kalatzis","year":"2004","unstructured":"Kalatzis V, Nevo N, Cherqui S, Gasnier B, Antignac C. Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin. Hum Mol Genet. 2004;13:1361\u201371. https:\/\/doi.org\/10.1093\/hmg\/ddh152.","journal-title":"Hum Mol Genet"},{"key":"1385_CR4","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13023-016-0426-y","volume":"11","author":"MA Elmonem","year":"2016","unstructured":"Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E. Cystinosis: a review. Orphanet J Rare Dis. 2016;11:47. https:\/\/doi.org\/10.1186\/s13023-016-0426-y.","journal-title":"Orphanet J Rare Dis"},{"key":"1385_CR5","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s00467-011-1942-6","volume":"27","author":"R Topaloglu","year":"2012","unstructured":"Topaloglu R, Vilboux T, Coskun T, Ozaltin F, Tinloy B, Gunay-Aygun M, et al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr Nephrol. 2012;27:115\u201321. https:\/\/doi.org\/10.1007\/s00467-011-1942-6.","journal-title":"Pediatr Nephrol"},{"key":"1385_CR6","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1007\/s00467-007-0650-8","volume":"23","author":"G Nesterova","year":"2008","unstructured":"Nesterova G, Gahl WA. Nephropathic cystinosis: late complications of a multisystemic disease. Pediatr Nephrol. 2008;23:863\u201378. https:\/\/doi.org\/10.1007\/s00467-007-0650-8.","journal-title":"Pediatr Nephrol"},{"key":"1385_CR7","doi-asserted-by":"publisher","first-page":"242","DOI":"10.7326\/0003-4819-147-4-200708210-00006","volume":"147","author":"WA Gahl","year":"2007","unstructured":"Gahl WA, Balog JZ, Kleta R. Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy. Ann Intern Med. 2007;147:242\u201350. https:\/\/doi.org\/10.7326\/0003-4819-147-4-200708210-00006.","journal-title":"Ann Intern Med"},{"key":"1385_CR8","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3389\/fped.2018.00058","volume":"6","author":"S B\u00e4umner","year":"2018","unstructured":"B\u00e4umner S, Weber LT. Nephropathic Cystinosis: symptoms, treatment, and perspectives of a systemic disease. Front Pediatr. 2018;6:58. https:\/\/doi.org\/10.3389\/fped.2018.00058.","journal-title":"Front Pediatr"},{"key":"1385_CR9","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.jpeds.2004.03.056","volume":"145","author":"R Kleta","year":"2004","unstructured":"Kleta R, Bernardini I, Ueda M, Varade WS, Phornphutkul C, Krasnewich D, et al. Long-term follow-up of well-treated nephropathic cystinosis patients. J Pediatr. 2004;145:555\u201360. https:\/\/doi.org\/10.1016\/j.jpeds.2004.03.056.","journal-title":"J Pediatr"},{"key":"1385_CR10","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1007\/s00467-010-1641-8","volume":"25","author":"M Greco","year":"2010","unstructured":"Greco M, Brugnara M, Zaffanello M, Taranta A, Pastore A, Emma F. Long-term outcome of nephropathic cystinosis: a 20-year single-center experience. Pediatr Nephrol. 2010;25:2459\u201367. https:\/\/doi.org\/10.1007\/s00467-010-1641-8.","journal-title":"Pediatr Nephrol"},{"key":"1385_CR11","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1159\/000245065","volume":"114","author":"MH Vaisbich","year":"2010","unstructured":"Vaisbich MH, Koch VH. Report of a Brazilian multicenter study on nephropathic cystinosis. Nephron Clin Pract. 2010;114:12\u20138. https:\/\/doi.org\/10.1159\/000245065.","journal-title":"Nephron Clin Pract"},{"issue":"Suppl 4","key":"1385_CR12","doi-asserted-by":"publisher","first-page":"iv87","DOI":"10.1093\/ndt\/gfu090","volume":"29","author":"F Emma","year":"2014","unstructured":"Emma F, Nesterova G, Langman C, Labb\u00e9 A, Cherqui S, Goodyer P, et al. Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant. 2014;29(Suppl 4):iv87\u201394. https:\/\/doi.org\/10.1093\/ndt\/gfu090.","journal-title":"Nephrol Dial Transplant"},{"key":"1385_CR13","doi-asserted-by":"publisher","first-page":"e428","DOI":"10.1111\/j.1440-1746.2008.05312.x","volume":"23","author":"T Cornelis","year":"2008","unstructured":"Cornelis T, Claes K, Gillard P, Nijs E, Roskams T, Lombaerts R, et al. Cholestatic liver disease in long-term infantile nephropathic cystinosis. J Gastroenterol Hepatol. 2008;23:e428\u201331. https:\/\/doi.org\/10.1111\/j.1440-1746.2008.05312.x.","journal-title":"J Gastroenterol Hepatol"},{"key":"1385_CR14","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1023\/B:BOLI.0000043028.97292.70","volume":"27","author":"P DiDomenico","year":"2004","unstructured":"DiDomenico P, Berry G, Bass D, Fridge J, Sarwal M. Noncirrhotic portal hypertension in association with juvenile nephropathic cystinosis: case presentation and review of the literature. J Inherit Metab Dis. 2004;27:693\u20139. https:\/\/doi.org\/10.1023\/B:BOLI.0000043028.97292.70.","journal-title":"J Inherit Metab Dis"},{"key":"1385_CR15","first-page":"879","volume":"7","author":"PJ Klenn","year":"1994","unstructured":"Klenn PJ, Rubin R. Hepatic fibrosis associated with hereditary cystinosis: a novel form of noncirrhotic portal hypertension. Mod Pathol. 1994;7:879\u201382.","journal-title":"Mod Pathol"},{"key":"1385_CR16","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s004670050467","volume":"12","author":"E Elenberg","year":"1998","unstructured":"Elenberg E, Norling LL, Kleinman RE, Ingelfinger JR. Feeding problems in cystinosis. Pediatr Nephrol. 1998;12:365\u201370.","journal-title":"Pediatr Nephrol"},{"key":"1385_CR17","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/S0887-8994(01)00268-5","volume":"24","author":"DA Trauner","year":"2001","unstructured":"Trauner DA, Fahmy RF, Mishler DA. Oral motor dysfunction and feeding difficulties in nephropathic cystinosis. Pediatr Neurol. 2001;24:365\u20138. https:\/\/doi.org\/10.1016\/S0887-8994(01)00268-5.","journal-title":"Pediatr Neurol"},{"key":"1385_CR18","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1097\/01.md.0000164204.00159.d4","volume":"84","author":"BC Sonies","year":"2005","unstructured":"Sonies BC, Almajid P, Kleta R, Bernardini I, Gahl WA. Swallowing dysfunction in 101 patients with nephropathic cystinosis: benefit of long-term cysteamine therapy. Medicine (Baltimore). 2005;84:137\u201346. https:\/\/doi.org\/10.1097\/01.md.0000164204.00159.d4.","journal-title":"Medicine (Baltimore)"},{"key":"1385_CR19","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1007\/s004670050009","volume":"14","author":"U Vester","year":"2000","unstructured":"Vester U, Schubert M, Offner G, Brodehl J. Distal myopathy in nephropathic cystinosis. Pediatr Nephrol. 2000;14:36\u20138.","journal-title":"Pediatr Nephrol"},{"key":"1385_CR20","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1002\/ana.410350209","volume":"35","author":"LR Charnas","year":"1994","unstructured":"Charnas LR, Luciano CA, Dalakas M, Gilliatt RW, Bernardini I, Ishak K, et al. Distal vacuolar myopathy in nephropathic cystinosis. Ann Neurol. 1994;35:181\u20138. https:\/\/doi.org\/10.1002\/ana.410350209.","journal-title":"Ann Neurol"},{"key":"1385_CR21","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1378\/chest.119.2.394","volume":"119","author":"Y Anikster","year":"2001","unstructured":"Anikster Y, Lacbawan F, Brantly M, Gochuico BL, Avila NA, Travis W, et al. Pulmonary dysfunction in adults with nephropathic cystinosis. Chest. 2001;119:394\u2013401. https:\/\/doi.org\/10.1378\/chest.119.2.394.","journal-title":"Chest."},{"key":"1385_CR22","unstructured":"Ulusoy M, Tun\u00e7bilek E. T\u00fcrkiye'de Akraba Evlilikleri ve \u00c7ocuk \u00f6l\u00fcmlerine Etkisi. Turkish J Popul Stud 1979\u20131988; Cumulative lndex to Volumes 1\u201310."},{"key":"1385_CR23","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/ki.2011.277","volume":"81","author":"A Brodin-Sartorius","year":"2012","unstructured":"Brodin-Sartorius A, T\u00eate MJ, Niaudet P, Antignac C, Guest G, Ottolenghi C, et al. Cysteamine therapy delays the progression of nephropathic cystinosis in late adolescents and adults. Kidney Int. 2012;81:179\u201389. https:\/\/doi.org\/10.1038\/ki.2011.277.","journal-title":"Kidney Int"},{"key":"1385_CR24","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1007\/s00467-014-3018-x","volume":"30","author":"G Nesterova","year":"2015","unstructured":"Nesterova G, Williams C, Bernardini I, Gahl WA. Cystinosis: renal glomerular and renal tubular function in relation to compliance with cystine-depleting therapy. Pediatr Nephrol. 2015;30:945\u201351. https:\/\/doi.org\/10.1007\/s00467-014-3018-x.","journal-title":"Pediatr Nephrol"},{"key":"1385_CR25","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1007\/s00467-009-1137-6","volume":"24","author":"P Cochat","year":"2009","unstructured":"Cochat P, Fargue S, Mestrallet G, Jungraithmayr T, Koch-Nogueira P, Ranchin B, et al. Disease recurrence in paediatric renal transplantation. Pediatr Nephrol. 2009;24:2097\u2013108. https:\/\/doi.org\/10.1007\/s00467-009-1137-6.","journal-title":"Pediatr Nephrol"},{"key":"1385_CR26","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s13023-015-0307-9","volume":"10","author":"C Cohen","year":"2015","unstructured":"Cohen C, Charbit M, Chadefaux-Vekemans B, Giral M, Garrigue V, Kessler M, et al. Excellent long-term outcome of renal transplantation in cystinosis patients. Orphanet J Rare Dis. 2015;10:90. https:\/\/doi.org\/10.1186\/s13023-015-0307-9.","journal-title":"Orphanet J Rare Dis"},{"key":"1385_CR27","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1101\/gr.10.2.165","volume":"10","author":"JW Touchman","year":"2000","unstructured":"Touchman JW, Anikster Y, Dietrich NL, Maduro VV, McDowell G, Shotelersuk V, et al. The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis causing deletion. Genome Res. 2000;10:165\u201373. https:\/\/doi.org\/10.1101\/gr.10.2.165.","journal-title":"Genome Res"},{"key":"1385_CR28","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/sj.ejhg.5200993","volume":"11","author":"S Mason","year":"2003","unstructured":"Mason S, Pepe G, Dall\u2019Amico R, Tartaglia S, Casciani S, Greco M, et al. Mutational spectrum of the CTNS gene in Italy. Eur J Hum Genet. 2003;11:503\u20138. https:\/\/doi.org\/10.1038\/sj.ejhg.5200993.","journal-title":"Eur J Hum Genet"},{"key":"1385_CR29","doi-asserted-by":"publisher","unstructured":"Topaloglu R, Gulhan B, \u0130n\u00f6z\u00fc M, Canpolat N, Yilmaz A, Noyan A, et al. The clinical and mutational spectrum of Turkish patients with cystinosis. Clin J Am Soc Nephrol. 2017 Aug 9. https:\/\/doi.org\/10.2215\/CJN.00180117.","DOI":"10.2215\/CJN.00180117"},{"key":"1385_CR30","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1002\/mus.26726","volume":"61","author":"R Sadjadi","year":"2020","unstructured":"Sadjadi R, Sullivan S, Grant N, Thomas SE, Doyle M, Hammond C, et al. Clinical myopathy in patients with Nephropathic Cystinosis. Muscle Nerve. 2020;61:74\u201380.","journal-title":"Muscle Nerve"},{"key":"1385_CR31","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1007\/s00467-015-3117-3","volume":"30","author":"MT Besouw","year":"2015","unstructured":"Besouw MT, Van Dyck M, Cassiman D, Claes KJ, Levtchenko EN. Management dilemmas in pediatric nephrology: Cystinosis. Pediatr Nephrol. 2015;30:1349\u201360. https:\/\/doi.org\/10.1007\/s00467-015-3117-3.","journal-title":"Pediatr Nephrol"}],"updated-by":[{"DOI":"10.1186\/s12876-022-02166-4","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000}}],"container-title":["BMC Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-020-01385-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12876-020-01385-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-020-01385-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T17:04:26Z","timestamp":1649178266000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcgastroenterol.biomedcentral.com\/articles\/10.1186\/s12876-020-01385-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,29]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1385"],"URL":"https:\/\/doi.org\/10.1186\/s12876-020-01385-x","relation":{},"ISSN":["1471-230X"],"issn-type":[{"value":"1471-230X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,29]]},"assertion":[{"value":"28 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2022","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s12876-022-02166-4","URL":"https:\/\/doi.org\/10.1186\/s12876-022-02166-4","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study protocol was approved by the Hacettepe University Ethics Committee (HEK 09\/134\u201342) and carried out in accordance with the Declaration of Helsinki. Written informed consent was obtained from the parents\/guardians of the minors included in this study. Minors are considered anyone under the age of 16. All patients consented to the study and publication.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The participants gave written informed consent for their personal or clinical details along with identifying images. Consent for publication was obtained from the parents\/guardians of the minors included in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"No financial or non-financial benefits have been received or will ve received from any party related directly or indirectly to the subject of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"242"}}