Hemoglobin O (HbO) is a rare type of

hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...

in which there is a substitution of

glutamic acid Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α- amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can ...

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

as in hemoglobin C, but at different positions. Since the amino acid substitution can occur at different positions of the β-globin chain of the protein, there are several variants. In hemoglobin O-Arab (HbO-Arab) substitution occurs at position 121, while in hemoglobin O-Padova (HbO-Padova) it is at 11 position, and in hemoglobin O Indonesia (HbO_Ina) it is at 116. HbO is usually harmless unlike other hemoglobin variants such as HbS and

thalassemia Thalassemias are a group of Genetic disorder, inherited blood disorders that manifest as the production of reduced hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe, including death. Often there is mild to ...

s, even under combination with these abnormal hemoglobins. Hemoglobin O-Padova is the most severe form and is associated with disease of the RBCs and spleen. __TOC__

Discovery

Hemoglobin O Indonesia is the first discovered HbO. Lie-Injo Luan Eng at the

University of Indonesia The University of Indonesia (UI; ) is a public university in Depok, West Java and Salemba, Jakarta, Indonesia. It is one of the oldest tertiary-level educational institutions in Indonesia (known as the Dutch East Indies when UI was established) ...

, Djakarta, was the first to notice the abnormal hemoglobin in 1956 among the

Buginese people The Bugis people, also known as Buginese, are an Austronesian peoples, Austronesian ethnic groupthe most numerous of the three major linguistic and ethnic groups of South Sulawesi (the others being Makassar people, Makassarese and Toraja peop ...

of Sulawesi Island in Indonesia. It was found among normal hemoblobin ( HbA) of the blood samples but different under

electrophoresis Electrophoresis is the motion of charged dispersed particles or dissolved charged molecules relative to a fluid under the influence of a spatially uniform electric field. As a rule, these are zwitterions with a positive or negative net ch ...

. It also showed different characters form HbS and HbC, and did not cause sickling of RBCs. The discovery went unnoticed as he later remarked, "This report, however, did not attract any attention as it was written in the Indonesian language." He again reported his observation in ''

The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal, founded in England in 1823. It is one of the world's highest-impact academic journals and also one of the oldest medical journals still in publication. The journal publishes ...

'' the next year. After consulting Hermann Lehmann at the

St Bartholomew's Hospital St Bartholomew's Hospital, commonly known as Barts, is a teaching hospital located in the City of London. It was founded in 1123 by Rahere, and is currently run by Barts Health NHS Trust. History Early history Barts was founded in 1123 by ...

in London and T.H.J. Huisman at the State University of Groningen in the Netherlands, and letting experimentally verified by Harvey Itano at the

California Institute of Technology The California Institute of Technology (branded as Caltech) is a private research university in Pasadena, California, United States. The university is responsible for many modern scientific advancements and is among a small group of institutes ...

, he was convinced that his discovery was a new type of hemoglobin. He gave the name "hemoglobin Buginese X" as he reported in '' The British Medical Journal'' in 1958, concluding:

As it has been confirmed by different laboratories that Buginese X differs from all other known haemoglobins, it should be allotted a letter. N was the letter most recently used to designate haemoglobin Liberian I (personal communication by Dr. James V. Neel). So far as we know, the letter 0 has not yet been used, and therefore Buginese X should be called Hb 0. Dr. James V. Neel agreed with this choice.

The same hemoglobin type was found in Iran in 1973. It was found that the protein modification was at position 116 where lysine was present in place of glutamic acid. In 1978, a similar case was reported from Italy. The hemoglobin was eventually named hemoglobin O Indonesia. In 1960, a different but related hemoglobin was found from an 8-year-old Arab boy at Jisr az-Zarqa in Israel. As the boy had severe pneumonia and blood abnormality (

hemoglobinopathy Hemoglobinopathy is the medical term for a group of inherited blood disorders involving the hemoglobin, the major protein of red blood cells. They are generally single-gene disorders and, in most cases, they are inherited as Autosome, autosomal R ...

) including sickled RBCs. His Hemoglobin was different from HbC and HbS and was designated as hemoglobin O (HbO). On investigating his family, his father was found to be the HbO carrier (i.e.

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

HbA/HbO) while her mother HbS carrier. Out of the six siblings, three had no HbO (though one has HbS), one had a heterozygous HbO. The boy and his older sister were diagnosed with sickle cell disease due to inherited HbS/HbO combination. It was later found that the amino acid replacement is at position 121 of the hemoglobin. The hemoglobin is now known as hemoglobin O-Arab. In 1974, another abnormal hemoglobin which they called hemoglobin O-Padova was identified from an Italian woman in Padova. It showed glutamic acid to lysine substitution at position 11. The woman was suffering from a complicated blood conditions. The mother and one of the two children indicated the same hemoglobin but without any symptom.

Disease

Hemoglobin O Indonesia is mostly harmless. But some individuals may indicate mild anemia. Even under heterozygous condition such as with HbD, no serious symptom is observed. With HbS, there can be mild

sickle cell trait Sickle cell trait describes a condition in which a person has one abnormal allele of the hemoglobin beta gene (is heterozygous), but does not display the severe symptoms of sickle cell disease that occur in a person who has two copies of that all ...

but no symptoms. Hemoglobin O-Arab causes sickle cell disease in heterozygous (HbS/HbO) individuals. However, the symptomatic anemia is mild and is not life-threatening. It is even milder than in heterozygous sickle cell trait (HbS/HbA). A case of

sickle cell retinopathy Sickle cell retinopathy can be defined as retinal changes due to blood vessel damage in the Human eye, eye of a person with a background of sickle cell disease. It can likely progress to loss of vision in late stages due to vitreous hemorrhage or r ...

is documented. Under

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

condition, it is also linked with

jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...

(conjugated hyperbilirubinemia), and mild anemia. Hemoglobin O-Padova in homozygous condition is associated with complex genetic and physiological anomalies. In the first woman diagnosed, severe RBC damage ( dyserythropoietic anemia), enlargement of spleen (

splenomegaly Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulat ...

), and abnormal RBC (hereditary erythroblastic multinuclearity). But heterozygous condition is clinically harmless.

References

{{Reflist Hemoglobins Blood disorders Genetic diseases and disorders