203:
494:
190:
29:
352:
326:) globin chains. In most HbM variants, the proximal (F8) or distal (E7) histidine residue is replaced by tyrosine. Proximal histidine (F8) is designated as position 87 in the alpha chain and 92 in the beta chain. Distal histidine (E7) is designated as position 58 in the alpha chain and position 63 in the beta chain.
431:, displaying an increased oxygen affinity. Normal beta subunits in alpha-chain variants (HbM Boston and HbM Iwate) exhibit reduced cooperativity and Bohr effect, displaying a decreased oxygen affinity. Hence, lower circulating oxidized Hb is observed in beta-chain variants than that in alpha-chain variants.
514:
Spectral absorption of the hemolysate at various wavelengths can be used for diagnosis. Compared with normal blood, a unique absorption range of HbM variants can be seen. HbM exhibits a specific light absorption pattern, shown by visible peaks at 510 and 630 nm. This explains the formation of
501:
It provides qualitative analysis by identification of abnormal Hb variants. Addition of KCN before electrophoresis converts all Hb types into metHb to prevent result misinterpretation due to iron state differences. Normal and abnormal Hb variants are separated by electric current, and the observed
334:
At least 13 HbM variants involving alpha- or beta- or gamma-chains have been reported. Six variants, namely HbM Boston, HbM Iwate, HbM Saskatoon, HbM Hyde Park, HbFM Osaka and HbFM Fort Ripley, manifest proximal (F8) or distal (E7) histidine substitution by tyrosine at position alpha-58, alpha-87,
403:
or chemical reduction. In HbM Boston (alpha-58 His→Tyr), new Tyr (E7) coordination alters the heme plane to disrupt the normal interaction between proximal His (F8) and heme iron. In HbM Iwate (alpha-87 His→Tyr), tyrosine coordination distorts the heme position. This increases the separation
407:
Oxygenated R (Relaxed) state (high-affinity Hb quaternary structure) is stabilized in beta-globin variants due to relaxed constraints between subunits. In HbM Saskatoon (beta-63 His→Tyr), substitution of a larger Tyr (E7) renders close proximity with heme ferric iron hence forming a
382:
ferrous iron. Stable covalent bond between tyrosine and Fe3+ hinders interaction between ferric iron and oxygen. Inability of ferric heme iron in binding oxygen alters oxygen affinity of ferrous heme iron in the remaining normal subunits, impeding oxygen delivery to body tissues.
502:
differences in migration indicate the substitution of the amino acid. For clear separation, hemoglobin electrophoresis should be performed on agar gel at pH 7.1. Under alkaline conditions, HbM migrates slightly slower than HbA. Further confirmatory testing can be performed by
459:
Exposure of venous blood samples to pure oxygen can be used to differentiate cyanosis caused by metHb from cardiopulmonary cyanosis or other cyanosis caused by low-O2 affinity Hbs. Cyanotic patients with methemoglobinemia display brownish blood while purple
210:
Cyanosis is the most common sign of hemoglobin M disease, which can be observed in all kinds of hemoglobin M diseases. It is mostly presented in the patient's lips and fingertips. Cyanosis in hemoglobin M disease results from elevated levels of metHb and
434:
For HbM Milwaukee-1 (beta-67 Val→Glu), proximity of anionic glutamate to the heme iron favors the autoxidation of ferrous iron and stabilization of ferric iron by direct coordination to its sixth coordinate position. This decreases oxygen affinity.
398:
Deoxygenated T (Tensed) state (low-affinity Hb quaternary structure) is stabilized in alpha-chain variants due to constraints between subunits. Ferric iron in alpha-chain variants show exceptional resistance to enzymatic reduction by
142:
There exists at least 13 HbM variants, such as Boston, Osaka, Saskatoon, etc., named according to their geographical locations of discovery. Different HbM variants may give different signs and symptoms. Major signs include
1357:
Rangan, Aruna; Savedra, Michelle E.; Dergam-Larson, Camila; Swanson, Kenneth C.; Szuberski, Jessica; Go, Ronald S.; Porter, Tavanna R.; Brunker, Sarah E.; Shi, Min; Nguyen, Phuong L.; Hoyer, James D. (August 2021).
484:
containing metHb with wild-type globin chains turn red immediately. The color change in hemolysates containing metHb with mutated globin chains is slower and the conversion rate for different HbM variants may vary.
215:(sulfHb). Dark brown blood is another major sign of hemoglobin M disease. Hemoglobin M diseases caused by different HbM variants may have slight variations in their signs and symptoms, some include signs such as
742:
Iolascon, Achille; Bianchi, Paola; Andolfo, Immacolata; Russo, Roberta; Barcellini, Wilma; Fermo, Elisa; Toldi, Gergely; Ghirardello, Stefano; Rees, Davis; Van Wijk, Richard; Kattamis, Antonis (2021-09-23).
531:
Automated fluorescence-based DNA sequence analysis is applied in the routine diagnosis of hemoglobinopathies as it provides a rapid and reliable result for the identification of specific globin gene
416:
of Tyr (E7) prompts enzymatic reduction by metHb reductase. In HbM Hyde Park (beta-92 His→Tyr), heme loss and instability with nearby residue reconstruction contribute to its pathophysiology.
1514:. Robert Kliegman, Bonita Stanton, Joseph W., III St. Geme, Nina Felice Schor, Richard E. Behrman, Waldo E. Preceded by: Nelson (Edition 21 ed.). Philadelphia, PA. 2020.
443:
Cyanosis caused by hemoglobin M disease is often mistaken as cardiac or pulmonary defects. Correct diagnosis is important to prevent unnecessary invasive procedures such as
1987:
493:
189:
370:
Tyrosine substitution renders structural alteration of the heme pocket and promotes spontaneous oxidation of heme iron from its ferrous state to
258:, and mild dyspnea at metHb level ranging from 10% to 30%. Other possible moderate signs and symptoms (metHb level above 30%) include dizziness,
1720:
1543:
1188:"Cyanosis, hemolysis, decreased HbA1c and abnormal co-oximetry in a patient with hemoglobin M Saskatoon [HBB:c.190C > T p.His64Tyr]"
555:
and it is not used to treat hemoglobin M disease. They are prone to develop symptomatic methemoglobinemia given further exposure to oxidants.
1691:. Stuart H. Orkin, David E. Fisher, David Ginsburg, A. Thomas Look, Samuel E. Lux, David G. Nathan (8th ed.). Philadelphia, PA. 2015.
543:
Hemoglobin M disease is often not life-threatening and treatment is not necessary. There is no existing effective treatment, including
247:. Infants with beta-globin variants become cyanotic around 6 months after birth with the completion of the fetal-to-adult Hb switch.
881:
Leung, Kwok Yin; Au, Patrick; Tang, Mary (2020-01-01), Pandya, Pranav P.; Oepkes, Dick; Sebire, Neil J.; Wapner, Ronald J. (eds.),
128:
503:
182:(CYB5R) deficiency is the major cause, rendering defective conversion of metHb to normal Hb. CYB5R deficiency is an autosomal
1992:
1696:
1563:"Hemoglobin M variant and congenital methemoglobinemia: methylene blue will not be effective in the presence of hemoglobin M"
1519:
1360:"Interpreting sulfhemoglobin and methemoglobin in patients with cyanosis: An overview of patients with M-hemoglobin variants"
1035:
894:
659:
160:
960:
Sangkitporn, S. K.; Eksiri, L.; Sangnoi, A.; Duangruang, S.; Dumbua, A.; Rattanakittisophon, K.; Sangkitporn, S. (2009).
167:
can be used for diagnosis. Hemoglobin M disease is often not life-threatening and there is no known effective treatment.
523:
in metHb detection. Pulse oximetry only uses two distinct wavelengths of 660 and 940 nm which can be misleading.
941:
1186:
Göttgens, Eva-Leonne; Baks, Kristian; Harteveld, Cornelis L.; Goossens, Kristel; van
Gammeren, Adriaan J. (2021).
962:"Identification of beta-globin gene mutations in Thailand using an automated fluorescence-based DNA sequencer"
472:(KCN) can be used to further distinguish hemoglobin M disease from other subtypes of methemoglobinemia and
423:
differ. Normal alpha subunits in beta-chain variants (HbM Saskatoon and HbM Hyde Park) exhibit significant
1023:
882:
647:
1724:
1547:
156:
67:
202:
1875:
Kim, Dae Sung; Baek, Hee Jo; Kim, Bo Ram; Yoon, Bo Ae; Lee, Jun Hyung; Kook, Hoon (December 2020).
646:
Randolph, Tim R. (2020-01-01), Keohane, Elaine M.; Otto, Catherine N.; Walenga, Jeanine M. (eds.),
378:
ion. Tyrosine can form an iron-phenolate complex with ferric iron which prevents reduction back to
228:
239:
variants. Infants with alpha- or gamma-chain variants manifest cyanosis since birth but transient
1934:"Hemoglobin M (Milwaukee) affects arterial oxygen saturation and makes pulse oximetry unreliable"
1452:
Rastogi, Loveena; Langer, Sabina; Radhakrishnan, Nita; Saxena, Renu; Kotwal, Jyoti (2020-09-30).
1118:
Patnaik, Sibabratta; Natarajan, Manivachagan
Muthappa; James, Ebor Jacob; Ebenezer, Kala (2014).
923:
824:
444:
400:
232:
179:
404:
between heme group and helix F within the altered alpha subunits for ferric iron stabilization.
1877:"The First Korean Family with Hemoglobin-M Milwaukee-2 Leading to Hereditary Methemoglobinemia"
448:
497:
Differences in skin colors and arterial blood colors between a normal individual and patients
302:
HbM is a rare methemoglobin group inherited in an autosomal dominant manner, resulting from
1815:
Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J. (March 2013).
1754:
823:
Picca, Andrew; Ruthford, Mason; Ghanim, Majd T.; Sims, Morgan; Kanter, Julie (2019-08-20).
387:
124:
8:
1758:
825:"Diagnosis of Hemoglobin M Disease in a Toddler Presenting With Hypoxemia and Hemolysis"
1909:
1876:
1849:
1816:
1714:
1600:
1537:
1486:
1453:
1395:
1292:
1235:
1154:
1119:
1090:
1057:
997:
860:
800:
787:
744:
709:
473:
275:
259:
212:
41:
1635:
193:
Pedigree chart of the patient's maternal family showing autosomal dominant inheritance
1963:
1955:
1950:
1933:
1914:
1896:
1854:
1836:
1790:
1785:
1772:
1742:
1702:
1692:
1647:
1639:
1592:
1584:
1525:
1515:
1491:
1473:
1434:
1426:
1399:
1387:
1379:
1339:
1331:
1284:
1276:
1271:
1254:
1239:
1227:
1219:
1159:
1141:
1095:
1077:
1031:
989:
981:
977:
937:
890:
864:
852:
844:
804:
792:
774:
701:
655:
614:
469:
303:
175:
62:
1604:
1296:
1001:
713:
367:
nitrogen of the proximal histidine (F8), and is able to bind to an oxygen molecule.
250:
Hemoglobin M disease is usually asymptomatic. However, it may show symptoms such as
1945:
1904:
1888:
1844:
1828:
1780:
1762:
1631:
1620:"Unstable hemoglobins, hemoglobins with altered oxygen affinity, and m-hemoglobins"
1574:
1481:
1465:
1371:
1323:
1266:
1209:
1199:
1149:
1131:
1085:
1069:
973:
929:
836:
782:
764:
756:
693:
244:
216:
96:
1204:
1187:
1311:
697:
461:
243:
cyanosis caused by gamma-chain variants resolves soon after the disappearance of
71:
1892:
1832:
1255:"Recessive congenital methaemoglobinaemia: cytochrome b(5) reductase deficiency"
1747:
Proceedings of the
National Academy of Sciences of the United States of America
606:
544:
520:
409:
335:
beta-63, beta-92, gamma-63 and gamma-92 respectively. HbM Milwaukee-1 involves
164:
108:
75:
1529:
1028:
Emery and Rimoin's
Principles and Practice of Medical Genetics (Sixth Edition)
155:, etc. Diagnosis is usually suspected based on cyanosis. Biochemical testing,
1981:
1959:
1900:
1840:
1776:
1706:
1643:
1588:
1477:
1430:
1415:"Clinical and laboratory features of two variants of methemoglobin M disease"
1383:
1335:
1280:
1223:
1145:
1136:
1081:
985:
848:
840:
778:
572:
548:
465:
424:
100:
1469:
1414:
1359:
961:
681:
28:
1967:
1918:
1858:
1794:
1767:
1619:
1596:
1509:
1495:
1438:
1391:
1288:
1231:
1163:
1099:
1073:
993:
856:
796:
705:
618:
263:
148:
132:
1686:
1651:
1454:"Hb-M Hyde Park: a rare cause of cyanosis arising from a de novo mutation"
1343:
1022:
Old, John (2013-01-01), Rimoin, David; Pyeritz, Reed; Korf, Bruce (eds.),
933:
516:
428:
413:
255:
224:
1214:
769:
1932:
Stucke, Astrid G.; Riess, Matthias L.; Connolly, Lois A. (April 2006).
1579:
1562:
1375:
375:
279:
171:
104:
1327:
760:
1817:"Hemoglobin Variants: Biochemical Properties and Clinical Correlates"
481:
419:
Physiological properties of non-mutant subunits within the mutant Hb
364:
340:
271:
251:
183:
120:
922:
Arceci, Robert J.; Hann, Ian M.; Smith, Owen P., eds. (2006-08-31).
509:
532:
420:
379:
287:
240:
144:
116:
99:, characterized by the presence of hemoglobin M (HbM) and elevated
46:
1688:
Nathan and Oski's hematology and oncology of infancy and childhood
959:
745:"Recommendations for diagnosis and treatment of methemoglobinemia"
351:
1356:
605:
Ludlow, John T.; Wilkerson, Richard G.; Nappe, Thomas M. (2022),
552:
477:
360:
283:
267:
152:
131:. The pathophysiology of hemoglobin M disease involves heme iron
1451:
393:
371:
336:
112:
386:
Stabilization of ferric iron is done through various abnormal
1185:
1117:
573:"Hemoglobin M disease (Concept Id: C3665425) – MedGen – NCBI"
220:
648:"24 - Hemoglobinopathies (structural defects in hemoglobin)"
741:
323:
319:
311:
307:
291:
236:
136:
682:"Hemoglobin M Disease as a Cause of Cyanosis in a Newborn"
1743:"A signature of the T → R transition in human hemoglobin"
315:
1741:
Mihailescu, Mihaela-Rita; Russu, Irina M. (2001-03-27).
1413:
Pisciotta, A. V.; Ebbe, S. N.; Hinz, J. E. (July 1959).
822:
390:
mechanisms between mutant side chains and ferric iron.
551:
used in treating acquired methemoglobinemia. MB is an
506:(HPLC) to provide quantification of the Hb fractions.
178:. For other congenital subtypes of methemoglobinemia,
1814:
604:
270:. More severe signs (metHb level above 50%) include
1931:
1312:"Congenital Methemoglobinemia Due to Hemoglobin M"
1024:"Chapter 71 - Hemoglobinopathies and Thalassemias"
679:
123:residues. HbM variants are inherited as autosomal
103:(metHb) level in blood. HbM is an altered form of
1412:
526:
510:Ultraviolet-Visible Wavelength Light Spectroscopy
346:
161:ultraviolet-visible wavelength light spectroscopy
1979:
1740:
1419:The Journal of Laboratory and Clinical Medicine
1120:"Methylene blue unresponsive methemoglobinemia"
921:
613:, Treasure Island (FL): StatPearls Publishing,
1874:
1617:
1561:Spears, Frances; Banerjee, Arnab (June 2008).
1560:
1364:International Journal of Laboratory Hematology
966:International Journal of Laboratory Hematology
654:, St. Louis (MO): Elsevier, pp. 394–423,
119:substitution for proximal (F8) or distal (E7)
535:. It is used as a further confirmatory test.
519:using multiple wavelengths is preferred over
488:
476:. For sulfhemoglobinemia, sulfHb is inert to
394:Mechanisms of Different Hemoglobin M Diseases
359:Under normal circumstances, the heme iron in
1253:Percy, Melanie J.; Lappin, Terry R. (2008).
1821:Cold Spring Harbor Perspectives in Medicine
1618:Vichinsky, E. P.; Lubin, B. H. (May 1980).
1252:
880:
1719:: CS1 maint: location missing publisher (
1542:: CS1 maint: location missing publisher (
883:"27 - Prenatal Screening for Thalassemias"
206:Cyanotic extremities and lip discoloration
1988:Disorders of globin and globulin proteins
1949:
1908:
1848:
1784:
1766:
1578:
1485:
1270:
1213:
1203:
1153:
1135:
1089:
1030:, Oxford: Academic Press, pp. 1–44,
889:, London: Elsevier, pp. 263–273.e1,
786:
768:
329:
1124:Indian Journal of Critical Care Medicine
686:Journal of Pediatric Hematology/Oncology
645:
492:
350:
201:
188:
151:or experience dizziness, headache, mild
1309:
36:Bluish fingertips in a cyanotic patient
1980:
1870:
1868:
1810:
1808:
1806:
1804:
1681:
1113:
1111:
1109:
1055:
504:high-performance liquid chromatography
454:
147:and dark brown blood. Patients may be
1736:
1734:
1679:
1677:
1675:
1673:
1671:
1669:
1667:
1665:
1663:
1661:
1181:
1179:
1177:
1175:
1173:
1017:
1015:
1013:
1011:
955:
953:
294:, and death (metHb level above 70%).
197:
917:
915:
913:
911:
876:
874:
818:
816:
814:
737:
735:
733:
731:
729:
727:
725:
723:
641:
639:
637:
635:
633:
600:
598:
596:
594:
592:
374:state (Fe3+) through discharge of a
363:state (Fe2+) is covalently bound to
1865:
1801:
1192:Hematology (Amsterdam, Netherlands)
1106:
1021:
13:
1731:
1658:
1624:Pediatric Clinics of North America
1170:
1008:
950:
652:Rodak's Hematology (Sixth Edition)
297:
115:-encoding genes, mostly involving
14:
2004:
908:
871:
811:
720:
630:
589:
227:. Onset of cyanosis varies among
1951:10.1097/00000542-200604000-00036
1272:10.1111/j.1365-2141.2008.07017.x
978:10.1111/j.1751-553X.2008.01072.x
27:
1925:
1611:
1567:Canadian Journal of Anaesthesia
1554:
1502:
1445:
1406:
1350:
1303:
1246:
1049:
680:Alonso-Ojembarrena, A. (2016).
1259:British Journal of Haematology
887:Fetal Medicine (Third Edition)
749:American Journal of Hematology
673:
565:
527:DNA-Based Globin Gene Analysis
347:Alterations in Oxygen Affinity
165:DNA-based globin gene analysis
139:pocket structural alteration.
1:
1636:10.1016/s0031-3955(16)33859-7
1511:Nelson textbook of pediatrics
1205:10.1080/16078454.2021.1999048
558:
343:residue at position beta-67.
1993:Hereditary hemolytic anemias
698:10.1097/MPH.0000000000000489
538:
480:and shows no colour change.
468:in other cases. Addition of
438:
7:
1893:10.3349/ymj.2020.61.12.1064
1833:10.1101/cshperspect.a011858
1062:Western Journal of Medicine
355:Normal hemoglobin structure
127:disorders and have altered
10:
2009:
489:Hemoglobin Electrophoresis
412:iron site where transient
170:Hemoglobin M disease is a
157:hemoglobin electrophoresis
68:Hemoglobin electrophoresis
1056:Rehman, Habib Ur (2001).
306:in genes encoding alpha (
82:
61:
53:
40:
35:
26:
21:
1137:10.4103/0972-5229.130582
928:. Blackwell Publishing.
841:10.1177/0009922819870555
86:No treatment is required
1470:10.5045/br.2020.2020084
515:chocolate-brown blood.
445:cardiac catheterization
180:cytochrome b5 reductase
1881:Yonsei Medical Journal
1768:10.1073/pnas.071493598
1074:10.1136/ewjm.175.3.193
498:
449:mechanical ventilation
356:
339:(E11) substitution by
330:Different HbM Variants
207:
194:
1723:) CS1 maint: others (
1546:) CS1 maint: others (
934:10.1002/9780470987001
496:
354:
205:
192:
57:Hemoglobin M variants
1310:Ă–zsoylu, S. (1972).
925:Pediatric Hematology
835:(11–12): 1345–1348.
577:www.ncbi.nlm.nih.gov
93:Hemoglobin M disease
49:and dark brown blood
22:Hemoglobin M disease
1759:2001PNAS...98.3773M
1058:"Methemoglobinemia"
829:Clinical Pediatrics
716:– via PubMed.
607:"Methemoglobinemia"
464:becomes bright red
455:Biochemical Testing
1580:10.1007/BF03021499
1376:10.1111/ijlh.13581
1316:Acta Haematologica
499:
474:sulfhemoglobinemia
357:
304:missense mutations
276:metabolic acidosis
208:
198:Signs and Symptoms
195:
95:is a rare form of
1887:(12): 1064–1067.
1698:978-0-323-29177-4
1521:978-0-323-56888-3
1328:10.1159/000208528
1037:978-0-12-383834-6
896:978-0-7020-6956-7
761:10.1002/ajh.26340
755:(12): 1666–1678.
661:978-0-323-53045-3
470:potassium cyanide
176:methemoglobinemia
90:
89:
63:Diagnostic method
16:Medical condition
2000:
1972:
1971:
1953:
1929:
1923:
1922:
1912:
1872:
1863:
1862:
1852:
1812:
1799:
1798:
1788:
1770:
1753:(7): 3773–3777.
1738:
1729:
1728:
1718:
1710:
1683:
1656:
1655:
1615:
1609:
1608:
1582:
1558:
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1207:
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1115:
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1005:
957:
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947:
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878:
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670:
669:
668:
643:
628:
627:
626:
625:
602:
587:
586:
584:
583:
569:
401:metHb reductases
217:hemolytic anemia
97:hemoglobinopathy
31:
19:
18:
2008:
2007:
2003:
2002:
2001:
1999:
1998:
1997:
1978:
1977:
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1975:
1930:
1926:
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1866:
1813:
1802:
1739:
1732:
1712:
1711:
1699:
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1684:
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1612:
1559:
1555:
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1534:
1522:
1508:
1507:
1503:
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1446:
1411:
1407:
1355:
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1308:
1304:
1251:
1247:
1184:
1171:
1116:
1107:
1054:
1050:
1042:
1040:
1038:
1020:
1009:
958:
951:
944:
920:
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901:
899:
897:
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872:
821:
812:
740:
721:
678:
674:
666:
664:
662:
644:
631:
623:
621:
603:
590:
581:
579:
571:
570:
566:
561:
541:
529:
512:
491:
462:deoxyhemoglobin
457:
441:
396:
349:
332:
300:
298:Pathophysiology
223:, and abnormal
200:
129:oxygen affinity
72:UV spectroscopy
17:
12:
11:
5:
2006:
1996:
1995:
1990:
1974:
1973:
1944:(4): 887–888.
1938:Anesthesiology
1924:
1864:
1827:(3): a011858.
1800:
1730:
1697:
1657:
1630:(2): 421–428.
1610:
1573:(6): 391–392.
1553:
1520:
1501:
1464:(3): 177–180.
1458:Blood Research
1444:
1405:
1370:(4): 837–844.
1349:
1322:(4): 225–232.
1302:
1265:(3): 298–308.
1245:
1198:(1): 914–918.
1169:
1130:(4): 253–255.
1105:
1068:(3): 193–196.
1048:
1036:
1007:
972:(5): 521–527.
949:
942:
907:
895:
870:
810:
719:
692:(3): 173–175.
672:
660:
629:
588:
563:
562:
560:
557:
545:methylene blue
540:
537:
528:
525:
521:pulse oximetry
511:
508:
490:
487:
456:
453:
440:
437:
410:hexacoordinate
395:
392:
348:
345:
331:
328:
299:
296:
262:, chest pain,
213:sulfhemoglobin
199:
196:
109:point mutation
88:
87:
84:
80:
79:
76:DNA sequencing
65:
59:
58:
55:
51:
50:
44:
38:
37:
33:
32:
24:
23:
15:
9:
6:
4:
3:
2:
2005:
1994:
1991:
1989:
1986:
1985:
1983:
1969:
1965:
1961:
1957:
1952:
1947:
1943:
1939:
1935:
1928:
1920:
1916:
1911:
1906:
1902:
1898:
1894:
1890:
1886:
1882:
1878:
1871:
1869:
1860:
1856:
1851:
1846:
1842:
1838:
1834:
1830:
1826:
1822:
1818:
1811:
1809:
1807:
1805:
1796:
1792:
1787:
1782:
1778:
1774:
1769:
1764:
1760:
1756:
1752:
1748:
1744:
1737:
1735:
1726:
1722:
1716:
1708:
1704:
1700:
1694:
1690:
1689:
1682:
1680:
1678:
1676:
1674:
1672:
1670:
1668:
1666:
1664:
1662:
1653:
1649:
1645:
1641:
1637:
1633:
1629:
1625:
1621:
1614:
1606:
1602:
1598:
1594:
1590:
1586:
1581:
1576:
1572:
1568:
1564:
1557:
1549:
1545:
1539:
1531:
1527:
1523:
1517:
1513:
1512:
1505:
1497:
1493:
1488:
1483:
1479:
1475:
1471:
1467:
1463:
1459:
1455:
1448:
1440:
1436:
1432:
1428:
1424:
1420:
1416:
1409:
1401:
1397:
1393:
1389:
1385:
1381:
1377:
1373:
1369:
1365:
1361:
1353:
1345:
1341:
1337:
1333:
1329:
1325:
1321:
1317:
1313:
1306:
1298:
1294:
1290:
1286:
1282:
1278:
1273:
1268:
1264:
1260:
1256:
1249:
1241:
1237:
1233:
1229:
1225:
1221:
1216:
1211:
1206:
1201:
1197:
1193:
1189:
1182:
1180:
1178:
1176:
1174:
1165:
1161:
1156:
1151:
1147:
1143:
1138:
1133:
1129:
1125:
1121:
1114:
1112:
1110:
1101:
1097:
1092:
1087:
1083:
1079:
1075:
1071:
1067:
1063:
1059:
1052:
1039:
1033:
1029:
1025:
1018:
1016:
1014:
1012:
1003:
999:
995:
991:
987:
983:
979:
975:
971:
967:
963:
956:
954:
945:
943:9780470987001
939:
935:
931:
927:
926:
918:
916:
914:
912:
898:
892:
888:
884:
877:
875:
866:
862:
858:
854:
850:
846:
842:
838:
834:
830:
826:
819:
817:
815:
806:
802:
798:
794:
789:
784:
780:
776:
771:
766:
762:
758:
754:
750:
746:
738:
736:
734:
732:
730:
728:
726:
724:
715:
711:
707:
703:
699:
695:
691:
687:
683:
676:
663:
657:
653:
649:
642:
640:
638:
636:
634:
620:
616:
612:
608:
601:
599:
597:
595:
593:
578:
574:
568:
564:
556:
554:
550:
549:ascorbic acid
546:
536:
534:
524:
522:
518:
507:
505:
495:
486:
483:
479:
475:
471:
467:
466:oxyhemoglobin
463:
452:
450:
446:
436:
432:
430:
426:
425:cooperativity
422:
417:
415:
411:
405:
402:
391:
389:
384:
381:
377:
373:
368:
366:
362:
353:
344:
342:
338:
327:
325:
321:
318:), or gamma (
317:
313:
309:
305:
295:
293:
289:
285:
281:
277:
273:
269:
265:
261:
257:
253:
248:
246:
242:
238:
234:
230:
226:
222:
218:
214:
204:
191:
187:
185:
181:
177:
173:
168:
166:
162:
158:
154:
150:
146:
140:
138:
134:
130:
126:
122:
118:
114:
111:occurring in
110:
106:
102:
101:methemoglobin
98:
94:
85:
81:
77:
73:
69:
66:
64:
60:
56:
52:
48:
45:
43:
39:
34:
30:
25:
20:
1941:
1937:
1927:
1884:
1880:
1824:
1820:
1750:
1746:
1687:
1627:
1623:
1613:
1570:
1566:
1556:
1510:
1504:
1461:
1457:
1447:
1425:(1): 73–87.
1422:
1418:
1408:
1367:
1363:
1352:
1319:
1315:
1305:
1262:
1258:
1248:
1215:1887/3249333
1195:
1191:
1127:
1123:
1065:
1061:
1051:
1041:, retrieved
1027:
969:
965:
924:
900:, retrieved
886:
832:
828:
770:1887/3249335
752:
748:
689:
685:
675:
665:, retrieved
651:
622:, retrieved
610:
580:. Retrieved
576:
567:
542:
530:
513:
500:
458:
442:
433:
418:
406:
397:
388:coordination
385:
369:
358:
333:
301:
264:palpitations
254:, headache,
249:
219:, decreased
209:
169:
149:asymptomatic
141:
135:promoted by
133:autoxidation
107:(Hb) due to
92:
91:
517:CO-oximetry
482:Hemolysates
429:Bohr effect
414:protonation
280:dysrhythmia
256:tachycardia
237:gamma-chain
225:co-oximetry
186:condition.
174:subtype of
1982:Categories
1530:1096283151
1043:2022-03-28
902:2022-03-28
667:2022-03-28
624:2022-03-28
611:StatPearls
582:2022-03-28
559:References
376:superoxide
172:congenital
105:hemoglobin
1960:0003-3022
1901:1976-2437
1841:2157-1422
1777:0027-8424
1715:cite book
1707:894113533
1644:0031-3955
1589:0832-610X
1538:cite book
1478:2287-979X
1431:0022-2143
1400:235362094
1384:1751-553X
1336:0001-5792
1281:1365-2141
1240:244346360
1224:1607-8454
1146:0972-5229
1082:0093-0415
986:1751-553X
865:201115221
849:0009-9228
805:237377613
779:0361-8609
547:(MB) and
539:Treatment
533:mutations
439:Diagnosis
365:imidazole
341:glutamate
314:), beta (
272:tachypnea
252:confusion
184:recessive
121:histidine
83:Treatment
1968:16571987
1919:33251782
1859:23388674
1795:11259676
1605:46308991
1597:18566207
1496:32747614
1439:13665153
1392:34092029
1297:36408296
1289:18318771
1232:34789072
1164:24872659
1100:11527852
1002:31589532
994:18498386
857:31431070
797:34467556
714:26848356
706:26694193
619:30726002
421:tetramer
380:divalent
288:delirium
245:fetal Hb
241:neonatal
145:cyanosis
125:dominant
117:tyrosine
47:Cyanosis
42:Symptoms
1910:7700874
1850:3579210
1755:Bibcode
1652:7383714
1487:7536569
1344:4625305
1155:4033863
1091:1071541
788:9291883
553:oxidant
478:cyanide
361:ferrous
284:seizure
268:fatigue
260:syncope
153:dyspnea
1966:
1958:
1917:
1907:
1899:
1857:
1847:
1839:
1793:
1783:
1775:
1705:
1695:
1650:
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1587:
1528:
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1484:
1476:
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1295:
1287:
1279:
1238:
1230:
1222:
1162:
1152:
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1080:
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1000:
992:
984:
940:
893:
863:
855:
847:
803:
795:
785:
777:
712:
704:
658:
617:
372:ferric
337:valine
266:, and
229:alpha-
163:, and
113:globin
78:, etc.
54:Causes
1786:31128
1601:S2CID
1396:S2CID
1293:S2CID
1236:S2CID
998:S2CID
861:S2CID
801:S2CID
710:S2CID
233:beta-
221:HbA1c
1964:PMID
1956:ISSN
1915:PMID
1897:ISSN
1855:PMID
1837:ISSN
1791:PMID
1773:ISSN
1725:link
1721:link
1703:OCLC
1693:ISBN
1648:PMID
1640:ISSN
1593:PMID
1585:ISSN
1548:link
1544:link
1526:OCLC
1516:ISBN
1492:PMID
1474:ISSN
1435:PMID
1427:ISSN
1388:PMID
1380:ISSN
1340:PMID
1332:ISSN
1285:PMID
1277:ISSN
1228:PMID
1220:ISSN
1160:PMID
1142:ISSN
1096:PMID
1078:ISSN
1032:ISBN
990:PMID
982:ISSN
938:ISBN
891:ISBN
853:PMID
845:ISSN
793:PMID
775:ISSN
702:PMID
656:ISBN
615:PMID
447:and
427:and
324:HBG2
320:HBG1
312:HBA2
308:HBA1
292:coma
235:and
137:heme
1946:doi
1942:104
1905:PMC
1889:doi
1845:PMC
1829:doi
1781:PMC
1763:doi
1632:doi
1575:doi
1482:PMC
1466:doi
1372:doi
1324:doi
1267:doi
1263:141
1210:hdl
1200:doi
1150:PMC
1132:doi
1086:PMC
1070:doi
1066:175
974:doi
930:doi
837:doi
783:PMC
765:hdl
757:doi
694:doi
316:HBB
1984::
1962:.
1954:.
1940:.
1936:.
1913:.
1903:.
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1885:61
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