{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:14:57Z","timestamp":1789773297106,"version":"4.0.1"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,3,2]],"date-time":"2018-03-02T00:00:00Z","timestamp":1519948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematology Reports"],"abstract":"<jats:p>Methemoglobinemia is a rare overlooked differential diagnosis in patients presented with cyanosis and dyspnea unrelated to cardiopulmonary causes. Our patient is 29 year old Indian non-smoker male, his story started 6 months prior to presentation to our center when he had generalized fatigue and discoloration of hands. He presented with persistent polycythemia with elevated hemoglobin level. The patient was misdiagnosed in another center as polycythemia and treated with Imatinib. The diagnosis of PV was revisited and ruled out in view of negative JAK2, normal erythropoietin level and absence of features of panmyelosis. Clinical cyanosis and lowoxygen saturation in the presence of normal arterial oxygen tension was highly suggestive of methemoglobinemia. Arterial blood gas revealed a methemoglobin level of 38% (normal: 0\u20131.5%). Cytochrome B5 reductase (Methemoglobin reductase B) was deficient at level of &lt;2.6 U\/g Hb) (normal: 6.6\u201313.3), consistent with methemoglobin reductase (cytochrome b5) deficiency and hence the diagnosis of congenital methemoglobinemia was established. The role of Imatinib in provoking methemoglobinemia is questionable and association between Imatinib and methemoglobinemia never described before. In our case, there were no other offending drugs in aggravating the patients\u2019 symptoms and cyanosis. The patient started on Vitamin C 500 mg once daily for which he responded well with less cyanosis and significant reduction of methemoglobin level. Congenital methemoglobinemia is a rare underreported hemoglobin disease and often clinically missed. Upon extensive review of English literature for cases of congenital methemoglobinemia due to deficiency of cytochrome b5 reductase, we found 23 cases diagnosed as type I (including the case reported here). 17 cases (~74%) of type I and 6 cases (27%) of type II. There is male predominance 73% versus 26% in females. Almost half of reported cases 12 cases (52%) are Indian, 2 Japanese, 3 English, 2 Arabic, one case Spanish and one case Italian. For type I, the median calculated age is 31 years with cyanosis and shortness of breath being the most common sign and symptoms. For type II: Six cases were reported in English literature, all in pediatric age group with median calculated age at presentation is 6 years with neurologic manifestations and mental retardation are the most common type II associated symptoms. Due to lack of systematic epidemiological studies, congenital methemoglobinemia is under diagnosed as it is under investigated and usually overlooked especially when presenting in adulthood and in absence of obvious acquired agents.<\/jats:p>","DOI":"10.4081\/hr.2018.7221","type":"journal-article","created":{"date-parts":[[2018,4,3]],"date-time":"2018-04-03T09:47:57Z","timestamp":1522748877000},"page":"7221","source":"Crossref","is-referenced-by-count":32,"title":["Congenital Methemoglobinemia Misdiagnosed as Polycythemia Vera: Case Report and Review of Literature"],"prefix":"10.3390","volume":"10","author":[{"given":"Dina Sameh","family":"Soliman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Yassin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,2]]},"reference":[{"key":"ref1","first-page":"2267","article-title":"The Metabolic and Molecular Basis of b5 reductase deficiency and enzymopenic hereditary methemoglobinemia","author":"Jaffe","year":"1995"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1097\/00000542-200111000-00041","article-title":"Severe oxyhemoglobin desaturation during induction of anesthesia in a patient with congenital methemoglobinemia","volume":"95","author":"Baraka","year":"2001","journal-title":"Anesthesiology"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/00000542-198901000-00021","article-title":"Effects of methemoglobinemia on pulse oximetry and mixed venous oximetry","volume":"70","author":"Barker","year":"1989","journal-title":"Anesthesiology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0952-8180(00)00113-6","article-title":"Methemoglobinemia after topical anesthesia with lidocaine and benzocaine for a difficult intubation","volume":"12","author":"Kern","year":"2000","journal-title":"J Clin Anesth"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.jclinane.2003.10.005","article-title":"Anesthetic management of a patient with congenital methemoglobinemia","volume":"16","author":"Maurtua","year":"2004","journal-title":"J Clin Anesth"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bcmd.2008.02.002","article-title":"Recessive hereditary methemoglobinemia: Two novel mutations in the NADH- cytochrome b5 reductase gene","volume":"41","author":"Fermo","year":"2008","journal-title":"Blood Cells Mol Dis"},{"key":"ref7","article-title":"Hemoglobinopathies in children","author":"Miller","year":"1980"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1365-2141.2008.07017.x","article-title":"Percy1 and Terry R. Lappin. Recessive congenital methaemoglobinaemia: cytochrome b5 reductase deficiency","volume":"141","author":"Melanie","year":"2008","journal-title":"Br J Hematol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/BF02535839","article-title":"Lipids of myelin, white matter and graymatter in a case of generalized deficiency of cytochrome b5 reductase in congenital methemoglobinemia with mental retardation","volume":"15","author":"Hirono","year":"1980","journal-title":"Lipids"},{"key":"ref10","first-page":"269","article-title":"Congenital methaemoglobinaemia: A rare cause of cyanosis in an adult patient","volume":"62","author":"Londhey","year":"2014","journal-title":"J Assoc Physicians India"},{"key":"ref11","first-page":"269","article-title":"congenital methemoglobinemia: a rare cause of cyanosis in an adult patient","volume":"62","author":"Shonola","year":"2014","journal-title":"J Assoc Physicians India"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1136\/bmj.1.4301.721","article-title":"Familial idopathic methaemoglobinaemia","author":"Deeny","year":"1943","journal-title":"Brit Med J"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1182\/blood.V44.6.879.879","article-title":"Methemoglobin reductase (cytochrome b5 reductase) deficiency in congenital methemoglobinemia","volume":"44","author":"13","year":"1974","journal-title":"Blood"},{"key":"ref14","first-page":"76","article-title":"Methemoglobinemia in a young man","volume":"35","author":"Hamirani","year":"2008","journal-title":"Tex Heart Inst J"},{"key":"ref15","first-page":"11","article-title":"A methemoglobinemia case who was previously diagnosed and treated as asthma","volume":"6","author":"Tasci","year":"2012","journal-title":"Respir Med Case Rep"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"108","DOI":"10.4103\/1658-5127.192983","article-title":"Hereditary methemoglobinemia manifesting in adolescence","volume":"7","author":"Badawi","year":"2016","journal-title":"J Appl Hematol"},{"key":"ref17","article-title":"Methemoglobinemia: a reappraisal with an Indian perspective","author":"Ramanamurthy"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s12291-016-0586-5","article-title":"Methemoglobinemia: living with dormant devil","volume":"32","author":"Trivedi","year":"2017","journal-title":"Indian J Clin Biochem"},{"key":"ref19","first-page":"1925","article-title":"Methemoglobinemia; a description of a case of NADH methemoglobulin reductase deficiency","volume":"72","author":"Gerli","year":"1981","journal-title":"Minerva Med"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1007\/s00277-012-1513-3","article-title":"Recessive congenital methemoglobinemia due to NADH-cytochrome b5 reductase deficiency associated with recurrent early pregnancy loss (REPL) in an Indian family","volume":"91","author":"Kedar","year":"2012","journal-title":"Ann Hematol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1182\/blood-2002-05-1405","article-title":"Familial idiopathic methemoglobinemia revisited: original cases reveal 2 novel mutations in NADHcytochrome b5 reductase","volume":"100","author":"Percy","year":"2002","journal-title":"Blood"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1159\/000207786","article-title":"Congenital methemoglobin-reductase (cytochrome b5 reductase) deficiency associated with mental retardation in a Spanish girl","volume":"59","author":"Vives-Corrons","year":"1978","journal-title":"Acta Haematol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/ajh.2830400411","article-title":"New variant of cytochrome b5 reductase deficiency (b5Rkurashiki) in red cells, platelets, lymphocytes, and cultured fibroblasts with congenital methemoglobinemia, mental and neurological retardation, and skeletal anomalies","volume":"40","author":"Yawata","year":"1992","journal-title":"Am J Hematol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/ajh.20368","article-title":"Congenital methemoglobinemia caused by Hb- MRatnagiri ((beta-63CAT\u2014>TAT, His\u2014>Tyr) in an Indian family","volume":"79","author":"Kedar","year":"2005","journal-title":"Am J Hematol"},{"key":"ref25","first-page":"19","article-title":"Congenital methemoglobinemia Type 2. 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