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'''Hemoglobin D''' ('''HbD''') is a [[Hemoglobin variants|variant of hemoglobin]], a protein complex that makes up [[red blood cells]]. Based on the locations of the original identification, it has been known by several names such as '''hemoglobin D-Los Angeles''', '''hemoglobin D-Punjab''',<ref name=":0">{{Cite journal |last1=Torres |first1=Lidiane de Souza |last2=Okumura |first2=Jéssika Viviani |last3=Silva |first3=Danilo Grünig Humberto da |last4=Bonini-Domingos |first4=Claudia Regina |date=March 2015 |title=Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis |journal=Revista Brasileira de Hematologia e Hemoterapia |language=en |volume=37 |issue=2 |pages=120–126 |doi=10.1016/j.bjhh.2015.02.007 |issn=1516-8484 |pmc=4382585 |pmid=25818823 |doi-access=free}}</ref> '''D-North Carolina''', '''D-Portugal''', '''D-Oak Ridge''', and '''D-Chicago.<ref name=":1">{{Cite journal |last1=El-Kalla |first1=S. |last2=Mathews |first2=A. R. |date=January 1997 |title=HB D-Punjab in the United Arab Emirates |url=http://dx.doi.org/10.3109/03630269709000669 |journal=Hemoglobin |volume=21 |issue=4 |pages=369–375 |doi=10.3109/03630269709000669 |issn=0363-0269 |pmid=9255615}}</ref>''' Hemoglobin D-Los Angeles was the first type identified by [[Harvey Itano]] in 1951, and was subsequently discovered that hemoglobin D-Punjab is the most abundant type that is common in the [[Sikhs]] of Punjab (of both Pakistan and India) and of Gujarat.<ref>{{Cite journal |last=Shekhda |first=Kalyan Mansukhbhai |date=2017 |title=Co-Inheritance of Haemoglobin D-Punjab and Beta Thalassemia - A Rare Variant |url=http://jcdr.net/article_fulltext.asp?issn=0973-709x&year=2017&volume=11&issue=6&page=OD21&issn=0973-709x&id=10114 |journal=Journal of Clinical and Diagnostic Research |volume=11 |issue=6 |pages=21–22 |doi=10.7860/JCDR/2017/27816.10114 |pmc=5535424 |pmid=28764232}}</ref>
'''Hemoglobin D''' ('''HbD''') is a [[Hemoglobin variants|variant of hemoglobin]], a protein complex that makes up [[red blood cells]]. Based on the locations of the original identification, it has been known by several names such as '''hemoglobin D-Los Angeles''', '''hemoglobin D-Punjab''',<ref name=":0">{{Cite journal |last1=Torres |first1=Lidiane de Souza |last2=Okumura |first2=Jéssika Viviani |last3=Silva |first3=Danilo Grünig Humberto da |last4=Bonini-Domingos |first4=Claudia Regina |date=March 2015 |title=Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis |journal=Revista Brasileira de Hematologia e Hemoterapia |language=en |volume=37 |issue=2 |pages=120–126 |doi=10.1016/j.bjhh.2015.02.007 |issn=1516-8484 |pmc=4382585 |pmid=25818823 |doi-access=free}}</ref> '''D-North Carolina''', '''D-Portugal''', '''D-Oak Ridge''', and '''D-Chicago.<ref name=":1">{{Cite journal |last1=El-Kalla |first1=S. |last2=Mathews |first2=A. R. |date=January 1997 |title=HB D-Punjab in the United Arab Emirates |url=http://dx.doi.org/10.3109/03630269709000669 |journal=Hemoglobin |volume=21 |issue=4 |pages=369–375 |doi=10.3109/03630269709000669 |issn=0363-0269 |pmid=9255615}}</ref>''' Hemoglobin D-Los Angeles was the first type identified by [[Harvey Itano]] in 1951, and was subsequently discovered that hemoglobin D-Punjab is the most abundant type that is common in the [[Sikhs]] of Punjab (of both Pakistan and India) and of Gujarat.<ref>{{Cite journal |last=Shekhda |first=Kalyan Mansukhbhai |date=2017 |title=Co-Inheritance of Haemoglobin D-Punjab and Beta Thalassemia - A Rare Variant |url=http://jcdr.net/article_fulltext.asp?issn=0973-709x&year=2017&volume=11&issue=6&page=OD21&issn=0973-709x&id=10114 |journal=Journal of Clinical and Diagnostic Research |volume=11 |issue=6 |pages=21–22 |doi=10.7860/JCDR/2017/27816.10114 |pmc=5535424 |pmid=28764232}}</ref>


Unlike normal adult human hemoglobin ([[Hemoglobin A|HbA]]) which has [[glutamic acid]] at its 121 amino acid position, it has [[glutamine]] instead.<ref name=":2">{{Citation |last=Randolph |first=Tim R. |title=Hemoglobinopathies (structural defects in hemoglobin) |date=2020 |work=Rodak's Hematology |pages=394–423 |url=https://linkinghub.elsevier.com/retrieve/pii/B9780323530453000337 |access-date=2024-02-29 |publisher=Elsevier |language=en |doi=10.1016/b978-0-323-53045-3.00033-7 |isbn=978-0-323-53045-3}}</ref> The single amino acid substitution can cause various [[blood diseases]], from fatal genetic anemia to mild [[hemolytic anemia]], an abnormal destruction of red blood cells.<ref name=":3">{{Cite journal |last=Shanthala Devi |first=A. M. |last2=Rameshkumar |first2=Karuna |last3=Sitalakshmi |first3=S. |date=2016 |title=Hb D: A Not So Rare Hemoglobinopathy |url=https://link.springer.com/article/10.1007/s12288-013-0319-3 |journal=Indian Journal of Hematology & Blood Transfusion: An Official Journal of Indian Society of Hematology and Blood Transfusion |volume=32 |issue=Suppl 1 |pages=294–298 |doi=10.1007/s12288-013-0319-3 |issn=0971-4502 |pmc=4925467 |pmid=27408416}}</ref> Depending on the type of genetic inheritance, it can produce four different conditions:<ref name=":2" /> heterozygous (inherited in only one of the chromosome 11) HbD trait, HbD-[[thalassemia]], HbS-D ([[Sickle cell disease|sickle cell]]) disease, and, very rarely, homozygous (inherited in both chromosome 11) HbD disease.<ref>{{Citation |last=Dasgupta |first=Amitava |title=Hemoglobinopathy |date=2014 |work=Clinical Chemistry, Immunology and Laboratory Quality Control |pages=363–390 |url=https://linkinghub.elsevier.com/retrieve/pii/B9780124078215000218 |access-date=2024-02-29 |publisher=Elsevier |language=en |doi=10.1016/b978-0-12-407821-5.00021-8 |isbn=978-0-12-407821-5 |last2=Wahed |first2=Amer}}</ref> It is the fourth most common hemoglobin variant after HbC, HbS, and HbO.<ref name=":3" />
Unlike normal adult human hemoglobin ([[Hemoglobin A|HbA]]) which has [[glutamic acid]] at its 121 amino acid position, it has [[glutamine]] instead.<ref name=":2">{{Citation |last=Randolph |first=Tim R. |title=Hemoglobinopathies (structural defects in hemoglobin) |date=2020 |work=Rodak's Hematology |pages=394–423 |url=https://linkinghub.elsevier.com/retrieve/pii/B9780323530453000337 |access-date=2024-02-29 |publisher=Elsevier |language=en |doi=10.1016/b978-0-323-53045-3.00033-7 |isbn=978-0-323-53045-3}}</ref> The single amino acid substitution can cause various [[blood diseases]], from fatal genetic anemia to mild [[hemolytic anemia]], an abnormal destruction of red blood cells.<ref name=":3">{{Cite journal |last=Shanthala Devi |first=A. M. |last2=Rameshkumar |first2=Karuna |last3=Sitalakshmi |first3=S. |date=2016 |title=Hb D: A Not So Rare Hemoglobinopathy |url=https://link.springer.com/article/10.1007/s12288-013-0319-3 |journal=Indian Journal of Hematology & Blood Transfusion: An Official Journal of Indian Society of Hematology and Blood Transfusion |volume=32 |issue=Suppl 1 |pages=294–298 |doi=10.1007/s12288-013-0319-3 |issn=0971-4502 |pmc=4925467 |pmid=27408416}}</ref> Depending on the type of genetic inheritance, it can produce four different conditions:<ref name=":2" /> heterozygous (inherited in only one of the chromosome 11) HbD trait, HbD-[[thalassemia]], HbS-D ([[Sickle cell disease|sickle cell]]) disease, and, very rarely, homozygous (inherited in both chromosome 11) HbD disease.<ref>{{Citation |last=Dasgupta |first=Amitava |title=Hemoglobinopathy |date=2014 |work=Clinical Chemistry, Immunology and Laboratory Quality Control |pages=363–390 |url=https://linkinghub.elsevier.com/retrieve/pii/B9780124078215000218 |access-date=2024-02-29 |publisher=Elsevier |language=en |doi=10.1016/b978-0-12-407821-5.00021-8 |isbn=978-0-12-407821-5 |last2=Wahed |first2=Amer}}</ref> It is the fourth hemoglobin type discovered after HbA, HbC and HbS;<ref name=":0" /> the third hemoglobin variant identified after HbC and HbS;'''<ref name=":1" />''' and the fourth most common hemoglobin variant after HbC, HbS, and HbO.<ref name=":3" />


== Structure ==
== Structure ==
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== Effects and symptoms ==
== Effects and symptoms ==
Hemoglobin in combination with normal hemoglobin (heterozygous HBD/HbA) is asymptomatic, causing no effects. Homozygous HbD/HbD causes mild hemolytic anemia and chronic non-progressive [[splenomegaly]] (enlargement of [[spleen]]).<ref name=":2" />
Hemoglobin in combination with normal hemoglobin (heterozygous HBD/HbA) is asymptomatic, causing no effects. Individuals have normal hemoglobin level and their red blood cells are normal spherical structure.<ref name=":4">{{Citation |last=Mallouh |first=Ahmad A. |title=Hemoglobinopathies-Non-Sickle Cell |date=2012 |work=Textbook of Clinical Pediatrics |pages=3023–3027 |editor-last=Elzouki |editor-first=Abdelaziz Y. |url=http://link.springer.com/10.1007/978-3-642-02202-9_325 |access-date=2024-02-29 |place=Berlin, Heidelberg |publisher=Springer Berlin Heidelberg |language=en |doi=10.1007/978-3-642-02202-9_325 |isbn=978-3-642-02201-2 |editor2-last=Harfi |editor2-first=Harb A. |editor3-last=Nazer |editor3-first=Hisham M. |editor4-last=Stapleton |editor4-first=F. Bruder}}</ref> Homozygous HbD/HbD causes mild hemolytic anemia and chronic non-progressive [[splenomegaly]] (enlargement of [[spleen]]).<ref name=":2" /> Heterozygous HbD/HbS causes sickel cell anemia. However, most cases of the disease are milder than the usual HbS/HbS conditions. The most serious complication noted is stroke. HbD-thalassemia cuases microcytic anemia which is generally milder that that in typical thalassemia.<ref name=":4" />


=== Management ===
=== Management ===
Hemoglobin D conditions such as homozygous and HbD/HbA heterozygous do not require medical intervention. HbD/HbS and HbD-thalassemia conditions are managed like the typical cases of sickle cell anemia and thalassemia. In case of sickle cell anemia, daily treatment with [[penicillin]] recommended up to five years of age.<ref>{{cite web |author=<!--Not stated--> |date=2014 |title=Evidence-Based Management of Sickle Cell Disease |url=https://www.nhlbi.nih.gov/sites/www.nhlbi.nih.gov/files/sickle-cell-disease-report.pdf |access-date=16 November 2017 |quote=twice-daily prophylactic penicillin beginning in early infancy and continuing through at least age 5}}</ref> Dietary supplementation of [[folic acid]] is recommended by the [[World Health Organization|WHO]].<ref name="WHO2011">{{cite web |date=January 2011 |title=Sickle-cell disease and other haemoglobin disorders Fact sheet N°308 |url=https://www.who.int/mediacentre/factsheets/fs308/en/ |url-status=dead |archive-url=https://web.archive.org/web/20160309034307/http://www.who.int/mediacentre/factsheets/fs308/en/ |archive-date=9 March 2016 |access-date=8 March 2016}}</ref> In 2019, [[Crizanlizumab]], a monoclonal antibody was approved by the United States FDA for reducing the frequency of blood vessel blockage in 16 years and older individuals.<ref>{{cite web |date=15 November 2019 |title=FDA approves crizanlizumab-tmca for sickle cell disease |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-crizanlizumab-tmca-sickle-cell-disease |access-date=12 December 2023 |publisher=U.S. Food and Drug Administration}}</ref> For thalassemia, regular lifelong [[Blood transfusion|blood transfusions]] is the usual treatment. [[Hematopoietic stem cell transplantation|Bone marrow transplants]] can be curative for some children.<ref name="pmid19678601">{{cite journal |last1=Muncie |first1=Herbert L. |last2=Campbell |first2=James S. |year=2009 |title=Alpha and Beta Thalassemia |url=http://www.aafp.org/link_out?pmid=19678601 |journal=American Family Physician |volume=80 |issue=4 |pages=339–44 |pmid=19678601}}</ref> Medications like [[deferoxamine]], [[deferiprone]] and [[luspatercept]].<ref name="Taher">{{cite journal |last1=Taher |first1=Ali T. |last2=Musallam |first2=Khaled M. |last3=Cappellini |first3=M. Domenica |date=25 February 2021 |title=β-Thalassemias |journal=New England Journal of Medicine |volume=384 |issue=8 |pages=727–743 |doi=10.1056/NEJMra2021838 |pmid=33626255 |s2cid=232049825}}</ref> [[Gene therapy]], [[exagamglogene autotemcel]] is approved for medical use in the United Kingdom since November 2023.<ref>{{cite press release |title=MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent β-thalassemia |website=[[Medicines and Healthcare products Regulatory Agency]] (MHRA) |date=16 November 2023 |url=https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia |access-date=8 December 2023 |archive-date=25 November 2023 |archive-url=https://web.archive.org/web/20231125015409/https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia |url-status=live}}</ref><ref name="Vertex PR">{{cite press release |title=Vertex and CRISPR Therapeutics Announce Authorization of the First CRISPR/Cas9 Gene-Edited Therapy, Casgevy (exagamglogene autotemcel), by the United Kingdom MHRA for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia |publisher=Vertex Pharmaceuticals |via=Business Wire |date=16 November 2023 |url=https://www.businesswire.com/news/home/20231115290500/en/%C2%A0Vertex-and-CRISPR-Therapeutics-Announce-Authorization-of-the-First-CRISPRCas9-Gene-Edited-Therapy-CASGEVY%E2%84%A2-exagamglogene-autotemcel-by-the-United-Kingdom-MHRA-for-the-Treatment-of-Sickle-Cell-Disease-and-Transfusion-Dependent-Beta-Thalassemia |access-date=9 December 2023 |archive-date=22 November 2023 |archive-url=https://web.archive.org/web/20231122154102/https://www.businesswire.com/news/home/20231115290500/en/%C2%A0Vertex-and-CRISPR-Therapeutics-Announce-Authorization-of-the-First-CRISPRCas9-Gene-Edited-Therapy-CASGEVY%E2%84%A2-exagamglogene-autotemcel-by-the-United-Kingdom-MHRA-for-the-Treatment-of-Sickle-Cell-Disease-and-Transfusion-Dependent-Beta-Thalassemia |url-status=live}}</ref>
Hemoglobin D conditions such as homozygous and HbD/HbA heterozygous do not require medical intervention. HbD/HbS and HbD-thalassemia conditions are managed like the typical cases of sickle cell anemia and thalassemia.<ref name=":4" /> In case of sickle cell anemia, daily treatment with [[penicillin]] recommended up to five years of age.<ref>{{cite web |author=<!--Not stated--> |date=2014 |title=Evidence-Based Management of Sickle Cell Disease |url=https://www.nhlbi.nih.gov/sites/www.nhlbi.nih.gov/files/sickle-cell-disease-report.pdf |access-date=16 November 2017 |quote=twice-daily prophylactic penicillin beginning in early infancy and continuing through at least age 5}}</ref> Dietary supplementation of [[folic acid]] is recommended by the [[World Health Organization|WHO]].<ref name="WHO2011">{{cite web |date=January 2011 |title=Sickle-cell disease and other haemoglobin disorders Fact sheet N°308 |url=https://www.who.int/mediacentre/factsheets/fs308/en/ |url-status=dead |archive-url=https://web.archive.org/web/20160309034307/http://www.who.int/mediacentre/factsheets/fs308/en/ |archive-date=9 March 2016 |access-date=8 March 2016}}</ref> In 2019, [[Crizanlizumab]], a monoclonal antibody was approved by the United States FDA for reducing the frequency of blood vessel blockage in 16 years and older individuals.<ref>{{cite web |date=15 November 2019 |title=FDA approves crizanlizumab-tmca for sickle cell disease |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-crizanlizumab-tmca-sickle-cell-disease |access-date=12 December 2023 |publisher=U.S. Food and Drug Administration}}</ref> For thalassemia, regular lifelong [[Blood transfusion|blood transfusions]] is the usual treatment. [[Hematopoietic stem cell transplantation|Bone marrow transplants]] can be curative for some children.<ref name="pmid19678601">{{cite journal |last1=Muncie |first1=Herbert L. |last2=Campbell |first2=James S. |year=2009 |title=Alpha and Beta Thalassemia |url=http://www.aafp.org/link_out?pmid=19678601 |journal=American Family Physician |volume=80 |issue=4 |pages=339–44 |pmid=19678601}}</ref> Medications like [[deferoxamine]], [[deferiprone]] and [[luspatercept]].<ref name="Taher">{{cite journal |last1=Taher |first1=Ali T. |last2=Musallam |first2=Khaled M. |last3=Cappellini |first3=M. Domenica |date=25 February 2021 |title=β-Thalassemias |journal=New England Journal of Medicine |volume=384 |issue=8 |pages=727–743 |doi=10.1056/NEJMra2021838 |pmid=33626255 |s2cid=232049825}}</ref> [[Gene therapy]], [[exagamglogene autotemcel]] is approved for medical use in the United Kingdom since November 2023.<ref>{{cite press release |title=MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent β-thalassemia |website=[[Medicines and Healthcare products Regulatory Agency]] (MHRA) |date=16 November 2023 |url=https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia |access-date=8 December 2023 |archive-date=25 November 2023 |archive-url=https://web.archive.org/web/20231125015409/https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia |url-status=live}}</ref><ref name="Vertex PR">{{cite press release |title=Vertex and CRISPR Therapeutics Announce Authorization of the First CRISPR/Cas9 Gene-Edited Therapy, Casgevy (exagamglogene autotemcel), by the United Kingdom MHRA for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia |publisher=Vertex Pharmaceuticals |via=Business Wire |date=16 November 2023 |url=https://www.businesswire.com/news/home/20231115290500/en/%C2%A0Vertex-and-CRISPR-Therapeutics-Announce-Authorization-of-the-First-CRISPRCas9-Gene-Edited-Therapy-CASGEVY%E2%84%A2-exagamglogene-autotemcel-by-the-United-Kingdom-MHRA-for-the-Treatment-of-Sickle-Cell-Disease-and-Transfusion-Dependent-Beta-Thalassemia |access-date=9 December 2023 |archive-date=22 November 2023 |archive-url=https://web.archive.org/web/20231122154102/https://www.businesswire.com/news/home/20231115290500/en/%C2%A0Vertex-and-CRISPR-Therapeutics-Announce-Authorization-of-the-First-CRISPRCas9-Gene-Edited-Therapy-CASGEVY%E2%84%A2-exagamglogene-autotemcel-by-the-United-Kingdom-MHRA-for-the-Treatment-of-Sickle-Cell-Disease-and-Transfusion-Dependent-Beta-Thalassemia |url-status=live}}</ref>


== Prevalence ==
== Prevalence ==
Hemoglobin D is most abundant among Sikhs, with occurrence of 2% in Punjab and 1% in Gujarat. It is also found in small number of individuals among Africans, Americans and Europeans who usually had close ethnicity with Indians in the past.<ref name=":3" /> It is below 2% among the African-Americans.<ref name=":2" /> Combination with β-thalassemia and HbS are known in south and east India; the first resulting in thalassemia and the latter in sickle cell anemia.<ref name=":3" /> Rare conditions like HbD/HbJ,<ref>{{Cite journal |last=Chandra |first=Dinesh |last2=Tyagi |first2=Seema |last3=Deka |first3=Roopam |last4=Chauhan |first4=Richa |last5=Seth |first5=Tulika |last6=Saxena |first6=Renu |last7=Pati |first7=H. P. |date=2017 |title=A Novel Double Heterozygous Hb D-Punjab/Hb J-Meerut Hemoglobinopathy |url=https://link.springer.com/article/10.1007/s12288-016-0763-y |journal=Indian Journal of Hematology & Blood Transfusion |volume=33 |issue=4 |pages=611–613 |doi=10.1007/s12288-016-0763-y |issn=0971-4502 |pmc=5640522 |pmid=29075078}}</ref> HbD/ HbQ,<ref>{{Cite journal |last=Parab |first=Sushama |last2=Sakhare |first2=Suhas |last3=Sengupta |first3=Caesar |last4=Velumani |first4=Arokiaswamy |date=2014 |title=Diagnosis of a rare double heterozygous Hb D Punjab/Hb Q India hemoglobinopathy using Sebia capillary zone electrophoresis |url=https://journals.lww.com/ijpm/fulltext/2014/57040/diagnosis_of_a_rare_double_heterozygous_hb_d.24.aspx |journal=Indian Journal of Pathology & Microbiology |volume=57 |issue=4 |pages=626–628 |doi=10.4103/0377-4929.142709 |issn=0974-5130 |pmid=25308024}}</ref> and HbD/Hb Fontainebleau<ref>{{Cite journal |last=Rodríguez-Capote |first=Karina |last2=Estey |first2=Mathew P. |last3=Barakauskas |first3=Vilte |last4=Bordeleau |first4=Pierre |last5=Christensen |first5=Cathie-Lou |last6=Zuberbuhler |first6=Peter |last7=Higgins |first7=Trefor N. |date=2015 |title=A novel double heterozygous Hb Fontainebleau/HbD Punjab hemoglobinopathy |url=https://www.sciencedirect.com/science/article/abs/pii/S0009912015002118?via%3Dihub |journal=Clinical Biochemistry |volume=48 |issue=13-14 |pages=904–907 |doi=10.1016/j.clinbiochem.2015.05.020 |issn=1873-2933 |pmid=26036869}}</ref> are also found in India. There is also high occurrence in China, with prevalence rate of 12.5% in [[Chongqing]].<ref>{{Cite journal |last=Li |first=Chun-Li |last2=Yang |first2=Mei |last3=Li |first3=Qiu-Hong |date=2020 |title=Analysis of 34 800 cases of Abnormal Hemoglobinopathy in Couples of Child-bearing Age in Chongqing Area |url= |journal=Zhongguo Shi Yan Xue Ye Xue Za Zhi |volume=28 |issue=4 |pages=1316–1320 |doi=10.19746/j.cnki.issn.1009-2137.2020.04.040 |issn=1009-2137 |pmid=32798419}}</ref>
Hemoglobin D is most abundant among Sikhs, with occurrence of 2% in Punjab and 1% in Gujarat. It is also found in small number of individuals among Africans, Americans and Europeans who usually had close ethnicity with Indians in the past.<ref name=":3" /> It is below 2% among the African-Americans.<ref name=":2" /> Combination with β-thalassemia and HbS are known in south and east India; the first resulting in thalassemia and the latter in sickle cell anemia.<ref name=":3" /> Rare conditions like HbD/HbJ,<ref>{{Cite journal |last=Chandra |first=Dinesh |last2=Tyagi |first2=Seema |last3=Deka |first3=Roopam |last4=Chauhan |first4=Richa |last5=Seth |first5=Tulika |last6=Saxena |first6=Renu |last7=Pati |first7=H. P. |date=2017 |title=A Novel Double Heterozygous Hb D-Punjab/Hb J-Meerut Hemoglobinopathy |url=https://link.springer.com/article/10.1007/s12288-016-0763-y |journal=Indian Journal of Hematology & Blood Transfusion |volume=33 |issue=4 |pages=611–613 |doi=10.1007/s12288-016-0763-y |issn=0971-4502 |pmc=5640522 |pmid=29075078}}</ref> HbD/ HbQ,<ref>{{Cite journal |last=Parab |first=Sushama |last2=Sakhare |first2=Suhas |last3=Sengupta |first3=Caesar |last4=Velumani |first4=Arokiaswamy |date=2014 |title=Diagnosis of a rare double heterozygous Hb D Punjab/Hb Q India hemoglobinopathy using Sebia capillary zone electrophoresis |url=https://journals.lww.com/ijpm/fulltext/2014/57040/diagnosis_of_a_rare_double_heterozygous_hb_d.24.aspx |journal=Indian Journal of Pathology & Microbiology |volume=57 |issue=4 |pages=626–628 |doi=10.4103/0377-4929.142709 |issn=0974-5130 |pmid=25308024}}</ref> and HbD/Hb Fontainebleau<ref>{{Cite journal |last=Rodríguez-Capote |first=Karina |last2=Estey |first2=Mathew P. |last3=Barakauskas |first3=Vilte |last4=Bordeleau |first4=Pierre |last5=Christensen |first5=Cathie-Lou |last6=Zuberbuhler |first6=Peter |last7=Higgins |first7=Trefor N. |date=2015 |title=A novel double heterozygous Hb Fontainebleau/HbD Punjab hemoglobinopathy |url=https://www.sciencedirect.com/science/article/abs/pii/S0009912015002118?via%3Dihub |journal=Clinical Biochemistry |volume=48 |issue=13-14 |pages=904–907 |doi=10.1016/j.clinbiochem.2015.05.020 |issn=1873-2933 |pmid=26036869}}</ref> are also found in India. There is also high occurrence in China, with prevalence rate of 12.5% in [[Chongqing]].<ref>{{Cite journal |last=Li |first=Chun-Li |last2=Yang |first2=Mei |last3=Li |first3=Qiu-Hong |date=2020 |title=Analysis of 34 800 cases of Abnormal Hemoglobinopathy in Couples of Child-bearing Age in Chongqing Area |url= |journal=Zhongguo Shi Yan Xue Ye Xue Za Zhi |volume=28 |issue=4 |pages=1316–1320 |doi=10.19746/j.cnki.issn.1009-2137.2020.04.040 |issn=1009-2137 |pmid=32798419}}</ref> It is sporadically recorded in some Turkish, Algerian, West African, Saudi Arabian, native American, English, and Irish population.<ref name=":4" />


== References ==
== References ==

Revision as of 12:37, 29 February 2024

Hemoglobin D
SpecialtyHematology
SymptomsHbD/HbA asymptomatic; HbD/HbD mild hemolytic anemia; HbD/HbS sickle cell anemia; HbD/Hb-thalassemia thalassemia
CausesPoint mutation in HBB gene
TreatmentNot required

Hemoglobin D (HbD) is a variant of hemoglobin, a protein complex that makes up red blood cells. Based on the locations of the original identification, it has been known by several names such as hemoglobin D-Los Angeles, hemoglobin D-Punjab,[1] D-North Carolina, D-Portugal, D-Oak Ridge, and D-Chicago.[2] Hemoglobin D-Los Angeles was the first type identified by Harvey Itano in 1951, and was subsequently discovered that hemoglobin D-Punjab is the most abundant type that is common in the Sikhs of Punjab (of both Pakistan and India) and of Gujarat.[3]

Unlike normal adult human hemoglobin (HbA) which has glutamic acid at its 121 amino acid position, it has glutamine instead.[4] The single amino acid substitution can cause various blood diseases, from fatal genetic anemia to mild hemolytic anemia, an abnormal destruction of red blood cells.[5] Depending on the type of genetic inheritance, it can produce four different conditions:[4] heterozygous (inherited in only one of the chromosome 11) HbD trait, HbD-thalassemia, HbS-D (sickle cell) disease, and, very rarely, homozygous (inherited in both chromosome 11) HbD disease.[6] It is the fourth hemoglobin type discovered after HbA, HbC and HbS;[1] the third hemoglobin variant identified after HbC and HbS;[2] and the fourth most common hemoglobin variant after HbC, HbS, and HbO.[5]

Structure

Hemoglobin D has the basic structure and composition of normal adult hemoglobin. It is a globular protein containing prosthetic (non-protein) group called heme. There are four individual peptide chains, namely two α- and two β-subunits, each made of 141 and 146 amino acid residues, respectively. One heme is associated with each chain and responsible for binding free oxygen in the blood. A single HbD is therefore a tetramer (containing four molecules), denoted as α2β2.[7] Each subunit has a molecular weight of about 16,000 Da (daltons), making the tetramer about 64,000 Da (64,458 g/mol) in size.[8] HbD is different from HbA only on the β-subunit where the amino acid glutamic acid at 121 position is replaced with glutamine (α2β2121Glu→Gln).[4] It has the same chemical characteristic as HbS (a hemoglobin of sickle cell trait), with one fewer negative charge at an alkaline pH than HbA. However, unlike HbS, it does not produce sickled RBC on its own under low level of oxygen.[4]

Effects and symptoms

Hemoglobin in combination with normal hemoglobin (heterozygous HBD/HbA) is asymptomatic, causing no effects. Individuals have normal hemoglobin level and their red blood cells are normal spherical structure.[9] Homozygous HbD/HbD causes mild hemolytic anemia and chronic non-progressive splenomegaly (enlargement of spleen).[4] Heterozygous HbD/HbS causes sickel cell anemia. However, most cases of the disease are milder than the usual HbS/HbS conditions. The most serious complication noted is stroke. HbD-thalassemia cuases microcytic anemia which is generally milder that that in typical thalassemia.[9]

Management

Hemoglobin D conditions such as homozygous and HbD/HbA heterozygous do not require medical intervention. HbD/HbS and HbD-thalassemia conditions are managed like the typical cases of sickle cell anemia and thalassemia.[9] In case of sickle cell anemia, daily treatment with penicillin recommended up to five years of age.[10] Dietary supplementation of folic acid is recommended by the WHO.[11] In 2019, Crizanlizumab, a monoclonal antibody was approved by the United States FDA for reducing the frequency of blood vessel blockage in 16 years and older individuals.[12] For thalassemia, regular lifelong blood transfusions is the usual treatment. Bone marrow transplants can be curative for some children.[13] Medications like deferoxamine, deferiprone and luspatercept.[14] Gene therapy, exagamglogene autotemcel is approved for medical use in the United Kingdom since November 2023.[15][16]

Prevalence

Hemoglobin D is most abundant among Sikhs, with occurrence of 2% in Punjab and 1% in Gujarat. It is also found in small number of individuals among Africans, Americans and Europeans who usually had close ethnicity with Indians in the past.[5] It is below 2% among the African-Americans.[4] Combination with β-thalassemia and HbS are known in south and east India; the first resulting in thalassemia and the latter in sickle cell anemia.[5] Rare conditions like HbD/HbJ,[17] HbD/ HbQ,[18] and HbD/Hb Fontainebleau[19] are also found in India. There is also high occurrence in China, with prevalence rate of 12.5% in Chongqing.[20] It is sporadically recorded in some Turkish, Algerian, West African, Saudi Arabian, native American, English, and Irish population.[9]

References

  1. ^ a b Torres, Lidiane de Souza; Okumura, Jéssika Viviani; Silva, Danilo Grünig Humberto da; Bonini-Domingos, Claudia Regina (March 2015). "Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis". Revista Brasileira de Hematologia e Hemoterapia. 37 (2): 120–126. doi:10.1016/j.bjhh.2015.02.007. ISSN 1516-8484. PMC 4382585. PMID 25818823.
  2. ^ a b El-Kalla, S.; Mathews, A. R. (January 1997). "HB D-Punjab in the United Arab Emirates". Hemoglobin. 21 (4): 369–375. doi:10.3109/03630269709000669. ISSN 0363-0269. PMID 9255615.
  3. ^ Shekhda, Kalyan Mansukhbhai (2017). "Co-Inheritance of Haemoglobin D-Punjab and Beta Thalassemia - A Rare Variant". Journal of Clinical and Diagnostic Research. 11 (6): 21–22. doi:10.7860/JCDR/2017/27816.10114. PMC 5535424. PMID 28764232.
  4. ^ a b c d e f Randolph, Tim R. (2020), "Hemoglobinopathies (structural defects in hemoglobin)", Rodak's Hematology, Elsevier, pp. 394–423, doi:10.1016/b978-0-323-53045-3.00033-7, ISBN 978-0-323-53045-3, retrieved 2024-02-29
  5. ^ a b c d Shanthala Devi, A. M.; Rameshkumar, Karuna; Sitalakshmi, S. (2016). "Hb D: A Not So Rare Hemoglobinopathy". Indian Journal of Hematology & Blood Transfusion: An Official Journal of Indian Society of Hematology and Blood Transfusion. 32 (Suppl 1): 294–298. doi:10.1007/s12288-013-0319-3. ISSN 0971-4502. PMC 4925467. PMID 27408416.
  6. ^ Dasgupta, Amitava; Wahed, Amer (2014), "Hemoglobinopathy", Clinical Chemistry, Immunology and Laboratory Quality Control, Elsevier, pp. 363–390, doi:10.1016/b978-0-12-407821-5.00021-8, ISBN 978-0-12-407821-5, retrieved 2024-02-29
  7. ^ Ahmed, Mostafa H.; Ghatge, Mohini S.; Safo, Martin K. (2020). "Hemoglobin: Structure, Function and Allostery". Sub-Cellular Biochemistry. 94: 345–382. doi:10.1007/978-3-030-41769-7_14. ISSN 0306-0225. PMC 7370311. PMID 32189307.
  8. ^ Palmer, Andre F.; Sun, Guoyong; Harris, David R. (2009). "Tangential flow filtration of hemoglobin". Biotechnology Progress. 25 (1): 189–199. doi:10.1002/btpr.119. ISSN 1520-6033. PMC 2647581. PMID 19224583.
  9. ^ a b c d Mallouh, Ahmad A. (2012), Elzouki, Abdelaziz Y.; Harfi, Harb A.; Nazer, Hisham M.; Stapleton, F. Bruder (eds.), "Hemoglobinopathies-Non-Sickle Cell", Textbook of Clinical Pediatrics, Berlin, Heidelberg: Springer Berlin Heidelberg, pp. 3023–3027, doi:10.1007/978-3-642-02202-9_325, ISBN 978-3-642-02201-2, retrieved 2024-02-29
  10. ^ "Evidence-Based Management of Sickle Cell Disease" (PDF). 2014. Retrieved 16 November 2017. twice-daily prophylactic penicillin beginning in early infancy and continuing through at least age 5
  11. ^ "Sickle-cell disease and other haemoglobin disorders Fact sheet N°308". January 2011. Archived from the original on 9 March 2016. Retrieved 8 March 2016.
  12. ^ "FDA approves crizanlizumab-tmca for sickle cell disease". U.S. Food and Drug Administration. 15 November 2019. Retrieved 12 December 2023.
  13. ^ Muncie, Herbert L.; Campbell, James S. (2009). "Alpha and Beta Thalassemia". American Family Physician. 80 (4): 339–44. PMID 19678601.
  14. ^ Taher, Ali T.; Musallam, Khaled M.; Cappellini, M. Domenica (25 February 2021). "β-Thalassemias". New England Journal of Medicine. 384 (8): 727–743. doi:10.1056/NEJMra2021838. PMID 33626255. S2CID 232049825.
  15. ^ "MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent β-thalassemia". Medicines and Healthcare products Regulatory Agency (MHRA) (Press release). 16 November 2023. Archived from the original on 25 November 2023. Retrieved 8 December 2023.
  16. ^ "Vertex and CRISPR Therapeutics Announce Authorization of the First CRISPR/Cas9 Gene-Edited Therapy, Casgevy (exagamglogene autotemcel), by the United Kingdom MHRA for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia" (Press release). Vertex Pharmaceuticals. 16 November 2023. Archived from the original on 22 November 2023. Retrieved 9 December 2023 – via Business Wire.
  17. ^ Chandra, Dinesh; Tyagi, Seema; Deka, Roopam; Chauhan, Richa; Seth, Tulika; Saxena, Renu; Pati, H. P. (2017). "A Novel Double Heterozygous Hb D-Punjab/Hb J-Meerut Hemoglobinopathy". Indian Journal of Hematology & Blood Transfusion. 33 (4): 611–613. doi:10.1007/s12288-016-0763-y. ISSN 0971-4502. PMC 5640522. PMID 29075078.
  18. ^ Parab, Sushama; Sakhare, Suhas; Sengupta, Caesar; Velumani, Arokiaswamy (2014). "Diagnosis of a rare double heterozygous Hb D Punjab/Hb Q India hemoglobinopathy using Sebia capillary zone electrophoresis". Indian Journal of Pathology & Microbiology. 57 (4): 626–628. doi:10.4103/0377-4929.142709. ISSN 0974-5130. PMID 25308024.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  19. ^ Rodríguez-Capote, Karina; Estey, Mathew P.; Barakauskas, Vilte; Bordeleau, Pierre; Christensen, Cathie-Lou; Zuberbuhler, Peter; Higgins, Trefor N. (2015). "A novel double heterozygous Hb Fontainebleau/HbD Punjab hemoglobinopathy". Clinical Biochemistry. 48 (13–14): 904–907. doi:10.1016/j.clinbiochem.2015.05.020. ISSN 1873-2933. PMID 26036869.
  20. ^ Li, Chun-Li; Yang, Mei; Li, Qiu-Hong (2020). "Analysis of 34 800 cases of Abnormal Hemoglobinopathy in Couples of Child-bearing Age in Chongqing Area". Zhongguo Shi Yan Xue Ye Xue Za Zhi. 28 (4): 1316–1320. doi:10.19746/j.cnki.issn.1009-2137.2020.04.040. ISSN 1009-2137. PMID 32798419.

External links

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