Hemoglobin E: Difference between revisions

{{Infobox medical condition (new)

| Namename = Hemoglobin E disease

| Imagesynonyms = Haemoglobin = E

| Captionimage = Hemoglobin E (Glu26Lys) 1yvt.png

| ICD10 pronounce = {{ICD10|D|58|2|d|55}}

| ICD9field = [[Hematology]]

| ICDO symptoms =

| OMIM complications =

| MedlinePlusonset =

| eMedicineSubjduration =

| eMedicineTopictypes =

| MeshIDcauses = D006446

[[File:Aminoacid chain normal Hb and HbE.pdf|right|thumb|First thirty amino acid of normal Hb (on top) and of HbE (down).]]'''Hemoglobin E''' or ('''haemoglobin EHbE''' (HbE) is an abnormal [[hemoglobin]] with a single point [[mutation]] in the β chain. At position 26 there is a change in the [[amino acid]], from [[glutamic acid]] to [[lysine]] (E26K). Hemoglobin E is very common among people of [[Southeast Asia]]n, [[Northeast India]]n, [[Sri Lanka]]n and [[Bangladesh]]i descent.<ref name="urmc.rochester.edu">{{Cite web | url=https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=160&ContentID=12 | title=Hemoglobin e Trait - Health Encyclopedia - University of Rochester Medical Center | access-date=2017-03-30 | archive-date=2017-08-30 | archive-url=https://web.archive.org/web/20170830191820/https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=160&ContentID=12 | url-status=live }}</ref><ref>{{Cite web |url=http://www.mhcs.health.nsw.gov.au/publicationsandresources/pdf/publication-pdfs/diseases-and-conditions/9095/oth-9095-eng.pdf |title=Archived copy |access-date=2017-06-08 |archive-url=https://web.archive.org/web/20140624052847/http://www.mhcs.health.nsw.gov.au/publicationsandresources/pdf/publication-pdfs/diseases-and-conditions/9095/oth-9095-eng.pdf |archive-date=2014-06-24 |url-status=dead }}</ref>

The βE mutation affects β-gene expression creating an alternate splicing site in the mRNA at codons 25-27 of the β-globin gene. Through this mechanism, there is a mild deficiency in normal β mRNA and production of small amounts of anomalous β mRNA. The reduced synthesis of β chain may cause [[beta-thalassemia|β-thalassemia]]. Also, this hemoglobin variant has a weak union between α- and β-globin, causing instability when there is a high amount of oxidant.<ref name=Chernoff>{{cite journal |vauthors=Chernoff AI, Minnich V, Nanakorn S, etal |title=Studies on hemoglobin E. I. The clinical, hematologic, and genetic characteristics of the hemoglobin E syndromes. |journal=J Lab Clin Med |volume=47 |issue=3 |pages=455–489 |year=1956 |pmid=13353880 |doi=}}</ref> HbE can be detected on [[electrophoresis]].

Hemoglobin E disease results when the offspring inherits the gene for HbE from both parents. At birth, babies [[homozygous]] for the hemoglobin E allele do not present symptoms duebecause tothey still have HbF ([[fetal hemoglobin]]) they still have. In the first months of life, fetal hemoglobin disappears and the amount of hemoglobin E increases, so the subjects start to have a mild β-thalassemia. People who are heterozygous for hemoglobin E (one normal allele and one abnormal allele) do not show any symptoms (there is usually no [[anemia]] or [[hemolysis]]). There are cases associated with haemolysis.<ref>A.V. Hoffbrand. Essential Haematology. Second edition. Page 69.</ref> Subjects homozygous for the hemoglobin E allele (two abnormal alleles) have a mild hemolytic anemia and mild [[splenomegaly|enlargement of the spleen]].

==HeterozygotesSickle-Hemoglobin forE HbEDisease and HbS(SE)==

Compound heterozygotes with hemoglobin sickle-hemoglobin E disease result when the gene of hemoglobin E is inherited from one parent and the gene for hemoglobin S from the other. As the amount of fetal hemoglobin decreases and hemoglobin S increases, a mild hemolytic anemia appears in the early stage of development. Patients with this disease experience some of the symptoms of [[File:HbESickle cell disease|sickle cell anemia]], including mild-moderate anemia, increased risk of infection, and painful betaThalassemiasickling traitcrises.pdf<ref>{{cite web |right|thumb|Hereditylast1=Arkansas Department of hemoglobinHealth |title=Sickle-Hemoglobin E Disease Fact Sheet |url=https:/β/www.healthy.arkansas.gov/images/uploads/sickle-thalassemia]]hemoglobin_e_disease.pdf |access-date=2020-02-28 |archive-date=2020-02-28 |archive-url=https://web.archive.org/web/20200228220925/https://www.healthy.arkansas.gov/images/uploads/sickle-hemoglobin_e_disease.pdf |url-status=live }}</ref>

[[File:HbE betaThalassemia trait.pdf|right|thumb|Heredity of hemoglobin E/β-thalassemia]] People who have hemoglobin E/β-thalassemia have inherited one gene for hemoglobin E from one parent and one gene for β-thalassemia from the other parent. Symptoms of Hemoglobin E/β-thalassemia canis rangea greatlysevere in severitydisease, largelyand dependingit onstill thehas natureno ofuniversal cure. However, the β-thalassemia mutation, andis itamenable stillto hasgenome noediting universalat curehigh efficiency in preclinical studies.<ref name=Weatherall>{{Citecite journal |lastlast1=FucharoenBadat |firstfirst1=SuthatM |last2=WeatherallEjaz |first2=DavidA |last3=Hua |first3=P |last4=Rice |first4=S |last5=Zhang |first5=W |last6=Hentges |first6=LD |last7=Fisher |first7=CA |last8=Denny |first8=N |last9=Schwessinger |first9=R |last10=Yasara |first10=N |last11=Roy |first11=NBA |last12=Issa |first12=F |last13=Roy |first13=A |last14=Telfer |first14=P |last15=Hughes |first15=J. |datelast16=2012-08-01Mettananda |titlefirst16=TheS Hemoglobin|last17=Higgs E|first17=DR Thalassemias|urllast18=http://perspectivesinmedicine.cshlp.org/content/2/8/a011734Davies |journalfirst18=ColdJOJ Spring|title=Direct Harborcorrection Perspectivesof inhaemoglobin E β-thalassaemia using base editors. Medicine|languagejournal=enNature Communications |date=19 April 2023 |volume=214 |issue=81 |pages=a0117342238 |doi=10.11011038/cshperspect.a011734|issn=2157s41467-1422023-37604-8 |pmid=2290819937076455|pmc=10115876 |bibcode=2023NatCo..14.2238B }}</ref> It affects more than a million people in the world.<ref name=Vichinsky>{{cite journal |author=Vichinsky E |title=Hemoglobin E Syndromes. |journal=Hematology Am Soc Hematol Educ Program |pages=79–83 |year=2007 |pmid=18024613 |doi=10.1182/asheducation-2007.1.79 |volume=2007|s2cid=10435042 |doi-access=free }}</ref> The consequencesSymptoms of hemoglobin E/β-thalassemia whenvary itbut iscan notinclude treatedgrowth canretardation, enlargement of the bespleen ([[heartsplenomegaly]]) failureand liver ([[hepatomegaly]]), [[hepatomegalyjaundice]], bone abnormalities, and cardiovascular problems.<ref name=Weatherall>{{Cite journal|enlargementlast1=Fucharoen|first1=Suthat|last2=Weatherall|first2=David J.|date=2012-08-01|title=The Hemoglobin E Thalassemias|journal=Cold Spring Harbor Perspectives in Medicine|language=en|volume=2|issue=8|pages=a011734|doi=10.1101/cshperspect.a011734|issn=2157-1422|pmid=22908199|pmc=3405827}}</ref> Recommended course of treatment depends on the liver]],nature problemsand inseverity of the bonessymptoms and may involve close monitoring of hemoglobin levels, etcfolic acid supplements, and potentially regular blood transfusions.<ref name=Weatherall />

There is a variety of genotypesphenotypes depending on the interaction of HbE and α-thalassemia. The presence of the α-thalassemia reduces the amount of HbE usually found in HbE heterozygotes. In other cases, in combination with certain thalassemia mutations, it provides an increased resistance to [[malaria]] (''[[P. falciparum]]'').<ref name=Bachir>{{Citation | lastlast1 = Bachir | firstfirst1 = D | last2 = Galacteros | first2 = F | title = Hemoglobin E disease. | publisher = Orphanet Encyclopedia | date = November 2004 | url = https://www.orpha.net/data/patho/GB/uk-HbE.pdf | accessdateaccess-date = January 13, 2014 | archive-date = March 4, 2016 | archive-url = https://web.archive.org/web/20160304205359/https://www.orpha.net/data/patho/GB/uk-HbE.pdf | url-status = dead }}</ref> This disease was first described by [[Virginia Minnich]] in 1954, who discovered a high prevalence of it in Thailand and initially referred to it as "Mediterranean Anaemia."<ref name=Weatherall />

Hemoglobin E is most prevalent in [[mainland Southeast Asia]] (Thailand, Myanmar, Cambodia, Laos, Vietnam<ref name=URMC>{{Citation | title = Hemoglobin E Trait | publisher = [[University of Rochester Medical Center]] | url = http://www.urmc.rochester.edu/Encyclopedia/Content.aspx?ContentTypeID=160&ContentID=12 | accessdateaccess-date = January 13, 2014}}</ref>), where[[Sri Lanka]], [[Northeast India]] and [[Bangladesh]]. In mainland Southeast Asia, its prevalence can reach 30 or 40%, and [[Northeast India]], where in certain areas it has carrier rates that reach 60% of the population. In Thailand the mutation can reach 50 or 70%, and it is higher in the northeast of the country. In Sri Lanka, it can reach up to 40% and affects those of [[Sinhalese people|Sinhalese]] and [[Vedda]] descent.<ref>{{Cite book | url=https://books.google.com/books?id=ywY_dN6ad8gC&printsec |title =frontcover#v Populations of the SAARC Countries: Bio-cultural Perspectives|isbn =onepage&q&f 9788120725621|last1 =false Sarkar|first1 = Jayanta|last2 = Ghosh|first2 = G. C.|year = 2003| publisher=Sterling Publishers Pvt. }}</ref><ref>http://php{{cite journal | last=Roychoudhury | first=Arun K.scripts.psu | last2=Nei | first2=Masatoshi | title=Genetic Relationships between Indians and Their Neighboring Populations | journal=Human Heredity | publisher=S.edu/nxm2/1985%20Publications/ Karger AG | volume=35 | issue=4 | year=1985 | issn=1423-roychoudhury-nei0062 | doi=10.pdf1159/000153545 | pages=201–206}}</ref> It is also found at high frequencies in Bangladesh and Indonesia.<ref>{{Cite book | url=https://books.google.com/books?id=2grSBwAAQBAJ&printsec |title =frontcover#v Genetic Disorders of the Indian Subcontinent|isbn =onepage&q&f 9781402022319|last1 =false Kumar|first1 = Dhavendra|date = 2012-09-15| publisher=Springer }}</ref><ref>{{cite journal|pmc=3237252 | pmid=22089616 | volume=134 | title=Hb E/beta-thalassaemia: a common & clinically diverse disorder | year=2011 | journal=Indian J. Med. Res. | pages=522–31 | authorvauthors=Olivieri NF, Pakbaz Z, Vichinsky E| issue=4 }}</ref> The trait can also appear in people of Turkish, Chinese and Filipino descent.<ref>https://www. name="urmc.rochester.edu"/encyclopedia/content.aspx?ContentTypeID=160&ContentID=12</ref> The mutation is estimated to have arisen within the last 5,000 years.<ref name=Ohashi>{{cite journal |author=Ohashi|title=Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection |journal=[[Am J Hum Genet]] |volume=74 |issue=6 |pages=1189–1208 |year=2004 |pmid=15114532 |doi=10.1086/421330 |pmc=1182083|display-authors=etal}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182083/pdf/AJHGv74p1198.pdf Free full text] {{Webarchive|url=https://web.archive.org/web/20230125184006/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182083/pdf/AJHGv74p1198.pdf |date=2023-01-25 }}</ref> In Europe, there have been found cases of families with hemoglobin E, but in these cases, the mutation differs from the one found in South-East Asia. This means that there may be different origins of the βE mutation.<ref name=Kazazian>{{cite journal |author=Kazazian HH, JR., Waber PG, Boehm CD, Lee JI, Antonarakis SE, Fairbanks VF. |title=Hemoglobin E in Europeans: Further Evidence for Multiple Origins of the βE-Globin Gene. |journal=[[Am J Hum Genet]] |volume=36 |issue=1 |pages=212–217 |year=1984 |pmid=6198908 |pmc=1684388}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1684388/pdf/ajhg00163-0214.pdf Free full text] {{Webarchive|url=https://web.archive.org/web/20230125184008/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1684388/pdf/ajhg00163-0214.pdf |date=2023-01-25 }}</ref><ref name=Bain>{{cite book| last = Bain | first = Barbara J | title = Blood cells: a practical guide | publisher = Wiley-Blackwell | edition = 4th | date = June 2006 | isbn = 978-1-4051-4265-6}}</ref>

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