{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T21:37:36Z","timestamp":1783201056140,"version":"3.54.6"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"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":["J Med Case Reports"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Introduction<\/jats:title>\n<jats:p>Hereditary hemochromatosis is an inherited disorder of iron metabolism, characterized by excessive iron deposition in major organs of the body, leading to multi-organ dysfunction. It is a genetically heterogeneous disease caused by mutations in one or more different genes, the most common being mutations in the <jats:italic>HFE<\/jats:italic> gene. <jats:italic>HFE<\/jats:italic> hereditary hemochromatosis is mostly found in Europeans and is almost always a result of two mutations: C282Y and H63D. The H63D mutation is not as penetrant as the C282Y mutation, but there are rare reported cases of hereditary hemochromatosis with homozygous H63D genotype. While the C282Y mutation is primarily confined to persons of Northern European origin, the H63D mutation is spread worldwide. Other types of hereditary hemochromatosis are rare and broadly defined as non-<jats:italic>HFE<\/jats:italic> hereditary hemochromatosis and include mutations in the hemojuvelin gene, hepcidin (<jats:italic>HAMP<\/jats:italic> gene), transferrin receptor 2 gene, and ferroportin gene.<\/jats:p>\n<jats:p>Hereditary hemochromatosis is commonly found in populations of European origin; in contrast, it is rare and less well understood in Asia. It can be masked by the presence of concurrent iron deficiency or secondary iron overload in thalassemias.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>We report the case of a 42-year-old Sri Lankan\u00a0man investigated for fatigue during a brief upper respiratory tract infection and found to have high liver transaminases and high serum ferritin, which persisted even after complete resolution of the infection. Homozygosity for H63D mutation in the <jats:italic>HFE<\/jats:italic> gene was detected. Liver enzymes, serum ferritin, and transferrin saturation normalized following venesections.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This case adds to the literature on the importance of being vigilant and investigating patients suspected for iron overload, including genetic studies for hereditary hemochromatosis, even though it is a rare clinical entity in Asians.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13256-020-02428-3","type":"journal-article","created":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T23:05:39Z","timestamp":1594249539000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transient elevation of serum ferritin in a Sri Lankan with homozygosity for H63D mutation in the HFE gene: a case report"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4079-1604","authenticated-orcid":false,"given":"Wasanthi","family":"Wickramasinghe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chathurika","family":"Karunathilaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saroj","family":"Jayasinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lallindra","family":"Gooneratne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"issue":"7","key":"2428_CR1","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1093\/clinchem\/47.7.1147","volume":"47","author":"E Lyon","year":"2001","unstructured":"Lyon E, Frank EL. Hereditary hemochromatosis since discovery of the HFE gene. Clin Chem. 2001;47(7):1147\u201356.","journal-title":"Clin Chem"},{"issue":"1","key":"2428_CR2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1182\/blood-2009-01-199109","volume":"114","author":"CY Lok","year":"2009","unstructured":"Lok CY, Merryweather-Clarke AT, Viprakasit V, Chinthammitr Y, Srichairatanakool S, Limwongse C, et al. Iron overload in the Asian community. Blood. 2009;114(1):20\u20135.","journal-title":"Blood."},{"key":"2428_CR3","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/ng0896-399","volume":"13","author":"JN Feder","year":"1996","unstructured":"Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, et al. A novel MHC class 1-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet. 1996;13:399\u2013408.","journal-title":"Nat Genet"},{"issue":"6","key":"2428_CR4","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1097\/MCG.0b013e3181919a33","volume":"43","author":"R Cheng","year":"2009","unstructured":"Cheng R, Barton JC, Kowdley KV. Differences in hepatic phenotype between hemochromatosis patients with HFE C282Y homozygosity and other HFE genotypes. J Clin Gastroenterol. 2009;43(6):569\u201373.","journal-title":"J Clin Gastroenterol"},{"key":"2428_CR5","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1093\/aje\/154.3.193","volume":"154","author":"EH Hanson","year":"2001","unstructured":"Hanson EH, Imperatore G, Burke W. HFE gene and hereditary hemochromatosis: a HuGE review. Hum Genome Epidemiol Am J Epidemiol. 2001;154:193\u2013206.","journal-title":"Hum Genome Epidemiol Am J Epidemiol"},{"key":"2428_CR6","first-page":"242","volume":"87","author":"MA Melis","year":"2002","unstructured":"Melis MA, Cau M, Deidda F, Barella S, Cao A, Galanello R. H63D mutation in the HFE gene increases iron overload in beta-thalassemia carriers. Haematologica. 2002;87:242\u20135.","journal-title":"Haematologica."},{"key":"2428_CR7","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/S0016-5085(99)70236-2","volume":"116","author":"L Kazemi-Shirazi","year":"1999","unstructured":"Kazemi-Shirazi L, Datz C, Maier-Dobersberger T, Kaserer K, Hackl F, Polli C, et al. The relation of iron status and hemochromatosis gene mutations in patients with chronic hepatitis C. Gastroenterology. 1999;116:127\u201334.","journal-title":"Gastroenterology."},{"key":"2428_CR8","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1136\/jmg.34.4.275","volume":"34","author":"AT Merryweather-Clarke","year":"1997","unstructured":"Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJ. Global prevalence of putative haemochromatosis mutations. J Med Genet. 1997;34:275\u20138.","journal-title":"J Med Genet"},{"key":"2428_CR9","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1089\/10906570050114902","volume":"4","author":"AT Merryweather-Clarke","year":"2000","unstructured":"Merryweather-Clarke AT, Pointon JJ, Jouanolle AM, Rochette J, Robson KJ. Geography of HFE C282Y and H63D mutations. Genet Test. 2000;4:183\u201398.","journal-title":"Genet Test"},{"key":"2428_CR10","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1006\/bcmd.2001.0451","volume":"27","author":"G Lucotte","year":"2001","unstructured":"Lucotte G, Champenois T, Semonin O. A rare case of a patient heterozygous for the hemochromatosis mutation C282Y and homozygous for H63D. Blood Cells Mol Dis. 2001;27:892\u20133.","journal-title":"Blood Cells Mol Dis"},{"key":"2428_CR11","doi-asserted-by":"publisher","first-page":"2502","DOI":"10.1182\/blood.V93.8.2502","volume":"93","author":"C Mura","year":"1999","unstructured":"Mura C, Raguenes O, F\u00e9rec C. HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood. 1999;93:2502\u20135.","journal-title":"Blood."},{"key":"2428_CR12","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1089\/10906570050114867","volume":"4","author":"JJ Pointon","year":"2000","unstructured":"Pointon JJ, Wallace D, Merryweather-Clarke AT, Robson KJ. Uncommon mutations and polymorphisms in the haemochromatosis gene. Genet Test. 2000;4:151\u201361.","journal-title":"Genet Test"},{"key":"2428_CR13","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1034\/j.1399-0004.2002.610108.x","volume":"61","author":"E Beutler","year":"2002","unstructured":"Beutler E, Griffin M, Gelbart T, West C. A previously undescribed nonsense mutation of the HFE gene. Clin Genet. 2002;61:40\u20132.","journal-title":"Clin Genet"},{"key":"2428_CR14","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1053\/gast.2002.31884","volume":"122","author":"M Steiner","year":"2002","unstructured":"Steiner M, Ocran K, Genschel J, Meier P, Gerl H, Ventz M, et al. A homozygous HFE gene splice site mutation (IVS5+1 G\/A) in a hereditary hemochromatosis patient of Vietnamese origin. Gastroenterology. 2002;122:789\u201395.","journal-title":"Gastroenterology."},{"key":"2428_CR15","first-page":"40","volume-title":"Postgraduate haematology","author":"C Camaschella","year":"2016","unstructured":"Camaschella C, Hoffbrand AV, Cappellini MD. Iron overload. In: Hoffbrand AV, Higgs DR, Keeling DM, Mehta AB, editors. Postgraduate haematology. 7th ed. Hoboken: Wiley Blackwell; 2016. p. 40\u201352.","edition":"7"},{"issue":"3","key":"2428_CR16","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/S0016-5085(02)80116-0","volume":"122","author":"PA Gochee","year":"2002","unstructured":"Gochee PA, Powell LW, Cullen DJ, Du Sart D, Rossi E, Olynyk JK. A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation. Gastroterology. 2002;122(3):646\u201351.","journal-title":"Gastroterology."},{"issue":"4","key":"2428_CR17","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1007\/s10620-006-3210-3","volume":"51","author":"J Samarasena","year":"2006","unstructured":"Samarasena J, Winsor W, Lush R, Duggan P, Xie Y, Borgaonkar M. Individuals homozygous for the H63D mutation have significantly elevated iron indexes. Dig Dis Sci. 2006;51(4):803\u20137.","journal-title":"Dig Dis Sci"},{"key":"2428_CR18","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1111\/j.1399-0004.2005.00563.x","volume":"69","author":"M Matas","year":"2006","unstructured":"Matas M, Guix P, Castro JA, Parera M, Ramon MM, Obrador A, et al. Prevalence of HFE C282Y and H63D in Jewish populations and clinical implications of H63D homozygosity. Clin Genet. 2006;69:155\u201362.","journal-title":"Clin Genet"},{"key":"2428_CR19","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1097\/00125817-200009000-00001","volume":"2","author":"W Burke","year":"2000","unstructured":"Burke W, Imperatore G, McDonnell SM, Baron RC, Khoury MJ. Contribution of different HFE genotypes to iron overload disease: A pooled analysis. Gene Med. 2000;2:271\u20137.","journal-title":"Gene Med"},{"key":"2428_CR20","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1006\/bcmd.1997.0148","volume":"23","author":"RL Sham","year":"1997","unstructured":"Sham RL, Ou CY, Cappuccio J, et al. Correlation between genotype and phenotype in hereditary hemochromatosis: analysis of 61 cases. Blood Cells Mol Dis. 1997;23:314\u201320.","journal-title":"Blood Cells Mol Dis"},{"key":"2428_CR21","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1136\/gut.43.3.441","volume":"43","author":"VF Fairbanks","year":"1998","unstructured":"Fairbanks VF, Brandhagen DJ, Thibodeau SN, Snow K, Wollan PC. H63D is an haemochromatosis associated allele. Gut. 1998;43:441\u20134.","journal-title":"Gut."},{"key":"2428_CR22","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1007\/s00277-008-0679-1","volume":"88","author":"P Pedersen","year":"2009","unstructured":"Pedersen P, Milman N. Genetic screening for HFE hemochromatosis in 6020 Danish men: penetrance of C282Y, H63D, and S65C variants. Ann Hematol. 2009;88:775\u201384.","journal-title":"Ann Hematol"},{"key":"2428_CR23","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/S0002-9297(07)64339-0","volume":"61","author":"E Beutler","year":"1997","unstructured":"Beutler E. The significance of the 187G (H63D) mutation in hemochromatosis. Am J Hum Genet. 1997;61:762\u20134.","journal-title":"Am J Hum Genet"},{"key":"2428_CR24","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1046\/j.1365-2141.2001.02949.x","volume":"114","author":"HA Jackson","year":"2001","unstructured":"Jackson HA, Carter K, Darke C, Guttridge MG, Ravine D, Hutton RD, et al. HFE mutations, iron deficiency and overload in 10,500 blood donors. Br J Haematol. 2001;114:474\u201384.","journal-title":"Br J Haematol"},{"key":"2428_CR25","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.7326\/0003-4819-130-12-199906150-00002","volume":"130","author":"BR Bacon","year":"1999","unstructured":"Bacon BR, Olynyk JK, Brunt EM, Britton RS, Wolff RK. HFE genotypes in hemochromatosis and other liver diseases. Ann Intern Med. 1999;130:1018\u20139.","journal-title":"Ann Intern Med"},{"issue":"4","key":"2428_CR26","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1155\/2014\/468521","volume":"28","author":"M Kelley","year":"2014","unstructured":"Kelley M, Joshi N, Borgaonkar M. Iron overload is rare in patients homozygous for the H63D mutation. Can J Gastroenerol Hepatol. 2014;28(4):198\u2013202.","journal-title":"Can J Gastroenerol Hepatol"},{"key":"2428_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.annepidem.2010.05.013","volume":"21","author":"AM Neghina","year":"2011","unstructured":"Neghina AM, Anghel A. Hemochromatosis genotypes and risk of iron overload \u2013 a meta-analysis. Ann Epidemiol. 2011;21:1\u201314.","journal-title":"Ann Epidemiol"},{"key":"2428_CR28","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1007\/s00277-010-0901-9","volume":"89","author":"N Aranda","year":"2010","unstructured":"Aranda N, Viteri FE, Montserrat C, Arija V. Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain. Ann Hematol. 2010;89:767\u201373.","journal-title":"Ann Hematol"},{"key":"2428_CR29","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/S0168-8278(99)80188-3","volume":"30","author":"P Brissot","year":"1999","unstructured":"Brissot P, Moirand R, Jouanolle AM, et al. A genotypic study of 217 unrelated probands diagnosed as \u201cgenetic hemochromatosis\u201d on \u201cclassical\u201d phenotypic criteria. J Hepatol. 1999;30:588\u201393.","journal-title":"J Hepatol"},{"key":"2428_CR30","unstructured":"Padeniya AGPM. Genetic modifiers of beta thalassaemia: phenotype-genotype relationship in a Sri Lankan Population [Doctoral dissertation]. Faculty of Medicine Colombo 2012."},{"issue":"4","key":"2428_CR31","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1086\/302318","volume":"64","author":"J Rochette","year":"1999","unstructured":"Rochette J, Pointon JJ, Fisher CA, Perera G, Arambepola M, Arichchi DS, et al. Multicentric origin of hemochromatosis gene (HFE) mutations. Am J Hum Genet. 1999;64(4):1056\u201362.","journal-title":"Am J Hum Genet"}],"container-title":["Journal of Medical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-020-02428-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13256-020-02428-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-020-02428-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T00:00:44Z","timestamp":1625788844000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmedicalcasereports.biomedcentral.com\/articles\/10.1186\/s13256-020-02428-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,9]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["2428"],"URL":"https:\/\/doi.org\/10.1186\/s13256-020-02428-3","relation":{},"ISSN":["1752-1947"],"issn-type":[{"value":"1752-1947","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,9]]},"assertion":[{"value":"30 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"93"}}