{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:53:18Z","timestamp":1785509598760,"version":"3.56.0"},"reference-count":17,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background: Cardiopulmonary disorders are the most common cause of central cyanosis, and methemoglobinemia is often overlooked in the differential diagnosis of patients with central cyanosis. In most cases, methemoglobinemia is acquired and hereditary congenital methemoglobinemia is rare. Only a few case reports of congenital methemoglobinemia can be found in PubMed. To date, only four cases of congenital methemoglobinemia diagnosed after the age of 50 years have been reported. Case Presentation: A 79-year-old Japanese woman presented at our hospital with the chief complaints of dyspnea and cyanosis. She exhibited cyanosis of the lips and extremities, and her SpO2 was 80%, with oxygen administration at 5 L\/min. Blood gas analysis revealed a PaO2 of 325.4 mmHg and methemoglobin level of 36.9%. The SpO2 and PaO2 values were dissociated, and methemoglobin levels were markedly elevated. Genetic analysis revealed a nonsynonymous variant in the gene encoding nicotinamide adenine dinucleotide cytochrome (NADH) B5 reductase 3 (CYB5R3), and the patient was diagnosed with congenital methemoglobinemia. Conclusions: It is important to consider methemoglobinemia in the differential diagnosis of patients with central cyanosis. At 79 years of age, our patient represents the oldest patient with this diagnosis. This report indicates that it is crucial to consider the possibility of methemoglobinemia regardless of the patient\u2019s age.<\/jats:p>","DOI":"10.3390\/medicina59030615","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T05:46:42Z","timestamp":1679291202000},"page":"615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hereditary Congenital Methemoglobinemia Diagnosed at the Age of 79 Years: A Case Report"],"prefix":"10.3390","volume":"59","author":[{"given":"Marohito","family":"Nakata","sequence":"first","affiliation":[{"name":"Department of Cardiology, Urasoe General Hospital, Urasoe 901-2132, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Urasoe General Hospital, Urasoe 901-2132, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Tabata","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Naha City Hospital, Naha 902-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Morikawa","sequence":"additional","affiliation":[{"name":"Division of Genomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7623-7969","authenticated-orcid":false,"given":"Hiroki","family":"Shibata","sequence":"additional","affiliation":[{"name":"Division of Genomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3120-6605","authenticated-orcid":false,"given":"Tsuneaki","family":"Kenzaka","sequence":"additional","affiliation":[{"name":"Division of Community Medicine and Career Development, Kobe University Graduate School of Medicine, Kobe 652-0032, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"ref_1","first-page":"799","article-title":"Exonic Point Mutations in NADH-Cytochrome B5 Reductase Genes of Homozygotes for Hereditary Methemoglobinemia, Types I and III: Putative Mechanisms of Tissue-Dependent Enzyme Deficiency","volume":"48","author":"Katsube","year":"1991","journal-title":"Am. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20416","DOI":"10.1016\/S0021-9258(19)88718-5","article-title":"Enzymatic Instability of NADH-Cytochrome b5 Reductase as a Cause of Hereditary Methemoglobinemia Type I (Red Cell Type)","volume":"267","author":"Shirabe","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102654","DOI":"10.1016\/j.jbc.2022.102654","article-title":"Cytochrome b5 Reductases: Redox Regulators of Cell Homeostasis","volume":"298","author":"Hall","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ullah, A., Shah, A.A., Syed, F., Mahmood, A., Ur Rehman, H., Khurshid, B., Samad, A., Ahmad, W., and Basit, S. (2023). Molecular Dynamic Simulation Analysis of a Novel Missense Variant in CYB5R3 Gene in Patients with Methemoglobinemia. Medicina, 59.","DOI":"10.3390\/medicina59020379"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7221","DOI":"10.4081\/hr.2018.7221","article-title":"Congenital Methemoglobinemia Misdiagnosed as Polycythemia Vera: Case Report and Review of Literature","volume":"10","author":"Soliman","year":"2018","journal-title":"Hematol. Rep."},{"key":"ref_6","first-page":"e14079","article-title":"Congenital Methemoglobinemia-Induced Cyanosis in Assault Victim","volume":"13","author":"Alotaibi","year":"2021","journal-title":"Cureus"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e236677","DOI":"10.1136\/bcr-2020-236677","article-title":"Congenital Methaemoglobinaemia Presenting in a 55-Year-Old Man","volume":"13","author":"Mead","year":"2020","journal-title":"BMJ Case Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1182\/blood.V95.10.3250","article-title":"A Novel Mutation in the NADH-Cytochrome b5 Reductase Gene of a Chinese Patient with Recessive Congenital Methemoglobinemia","volume":"95","author":"Wang","year":"2000","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1053\/j.jvca.2012.12.010","article-title":"Late Diagnosis of Congenital Methemoglobinemia in an Elderly Patient During Cardiac Surgery","volume":"28","author":"Champigneulle","year":"2014","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1056\/NEJMcpc049013","article-title":"Case Records of the Massachusetts General Hospital. Weekly Clinicopathological Exercises. Case 23-2004. A 50-Year-Old Woman with Low Oxygen Saturation","volume":"351","author":"Hurford","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1213\/00000539-198903000-00035","article-title":"Principles of Pulse Oximetry: Theoretical and Practical Considerations","volume":"68","author":"Alexander","year":"1989","journal-title":"Anesth. Analg."},{"key":"ref_12","unstructured":"Post, T.W., Burns, M.M., Burns, M.M., and Tirnauer, J.S. (2022). UpToDate\u00ae, Wolters Kluwer. Available online: https:\/\/www.uptodate.com\/contents\/methemoglobinemia?search=Methemoglobinemia&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1182\/blood.V114.22.2588.2588","article-title":"Type I Methemoglobinemia Caused by the Cytochrome b5 Reductase 806C>T Mutation Is Present in the Indigenous Evenk People of Yakutia","volume":"114","author":"Burtseva","year":"2009","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1182\/blood.V13.8.795.795","article-title":"Hereditary Methemoglobinemia in Alaskan Eskimos and Indians","volume":"13","author":"Scott","year":"1958","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1172\/JCI104131","article-title":"The Relation of Diaphorase of Human Erythrocytes to Inheritance of Methemoglobinemia","volume":"39","author":"Scott","year":"1960","journal-title":"J. Clin. Investig."},{"key":"ref_16","first-page":"57","article-title":"Studies on the Congenital Methemoglobinemia in Okinawa Islands. 3. Mass Survey on Henza and Miyagi Islands","volume":"26","author":"Kiyama","year":"1973","journal-title":"Kumamoto Med. J."},{"key":"ref_17","first-page":"211","article-title":"Studies on the Congenital Methemoglobinemia in Okinawa Island. II. Diaphorase Activity","volume":"19","author":"Kawakita","year":"1966","journal-title":"Kumamoto Med. J."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/3\/615\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:59:15Z","timestamp":1760122755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/3\/615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,20]]},"references-count":17,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["medicina59030615"],"URL":"https:\/\/doi.org\/10.3390\/medicina59030615","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,20]]}}}