Hemoglobin E (HbE) is an abnormal

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 ...

with a single point

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

in the β chain. At position 26 there is a change in the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

, from

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 ( ...

(E26K). Hemoglobin E is very common among people of

Southeast Asia Southeast Asia is the geographical United Nations geoscheme for Asia#South-eastern Asia, southeastern region of Asia, consisting of the regions that are situated south of China, east of the Indian subcontinent, and northwest of the Mainland Au ...

Northeast India Northeast India, officially the North Eastern Region (NER), is the easternmost region of India representing both a geographic and political Administrative divisions of India, administrative division of the country. It comprises eight States and ...

Sri Lanka Sri Lanka, officially the Democratic Socialist Republic of Sri Lanka, also known historically as Ceylon, is an island country in South Asia. It lies in the Indian Ocean, southwest of the Bay of Bengal, separated from the Indian subcontinent, ...

n and

Bangladesh Bangladesh, officially the People's Republic of Bangladesh, is a country in South Asia. It is the List of countries and dependencies by population, eighth-most populous country in the world and among the List of countries and dependencies by ...

i descent. 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

β-thalassemia Beta-thalassemia (β-thalassemia) is an inherited blood disorder, a form of thalassemia resulting in variable outcomes ranging from clinically asymptomatic to severe anemia individuals. It is caused by reduced or absent synthesis of the beta ...

. Also, this hemoglobin variant has a weak union between α- and β-globin, causing instability when there is a high amount of oxidant. HbE can be detected on

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 ...

Hemoglobin E disease (EE)

Hemoglobin E disease results when the offspring inherits the gene for HbE from both parents. At birth, babies

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 ...

for the hemoglobin E allele do not present symptoms because they still have HbF (

fetal hemoglobin Fetal hemoglobin, or foetal haemoglobin (also hemoglobin F, HbF, or α2γ2) is the main oxygen carrier protein in the human fetus. HemoglobinF is found in fetal red blood cells, and is involved in transporting oxygen from the mother's bloodstream ...

). 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. Subjects homozygous for the hemoglobin E allele (two abnormal alleles) have a mild hemolytic anemia and mild enlargement of the spleen.

Hemoglobin E trait: heterozygotes for HbE (AE)

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 ...

AE occurs when the gene for hemoglobin E is inherited from one parent and the gene for hemoglobin A from the other. This is called hemoglobin E trait, and it is not a disease. People who have hemoglobin E trait (heterozygous) are asymptomatic and their state does not usually result in health problems. They may have a low

mean corpuscular volume The mean corpuscular volume, or mean cell volume (MCV), is a measure of the average volume of a red blood corpuscle (or red blood cell). The measure is obtained by multiplying a volume of blood by the proportion of blood that is cellular (the hem ...

(MCV) and very abnormal red blood cells (

target cells Codocytes, also known as target cells, are red blood cells that have the appearance of a shooting target with a bullseye (target), bullseye. In optical microscopy these cells appear to have a dark center (a central, hemoglobinized area) surrounde ...

), but clinical relevance is mainly due to the potential for transmitting E or β-thalassemia.

Sickle-Hemoglobin E Disease (SE)

Compound heterozygotes with 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

sickle cell anemia Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the oxygen-carrying ...

, including mild-moderate anemia, increased risk of infection, and painful sickling crises.

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

from the other parent; affecting more than a million people in the world. Symptoms of hemoglobin E/β-thalassemia vary widely in severity, from mild anemia to full thalassemia major; they can include growth retardation, enlargement of the 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 liver (

hepatomegaly Hepatomegaly is enlargement of the liver. It is a non-specific sign (medicine), medical sign, having many causes, which can broadly be broken down into infection, hepatic tumours, and metabolic disorder. Often, hepatomegaly presents as an abdomin ...

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 ...

, bone abnormalities, and cardiovascular problems. Recommended course of treatment depends on the nature and severity of the symptoms and may involve close monitoring of hemoglobin levels, folic acid supplements, and potentially regular blood transfusions.

Epidemiology

Hemoglobin E is most prevalent in

mainland Southeast Asia Mainland Southeast Asia (historically known as Indochina and the Indochinese Peninsula) is the continental portion of Southeast Asia. It lies east of the Indian subcontinent and south of Mainland China and is bordered by the Indian Ocean to th ...

(Thailand, Myanmar, Cambodia, Laos, Vietnam),

and

. In mainland Southeast Asia, its prevalence can reach 30 or 40%, and

, 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 and

Vedda The Vedda ( ; (''Vēḍar'')), or Wanniyalaeto, are a minority indigenous group of people in Sri Lanka who, among other sub-communities such as Coast Veddas, Anuradhapura Veddas and Bintenne Veddas, are accorded indigenous status. The Ved ...

descent. It is also found at high frequencies in Bangladesh and Indonesia. The trait can also appear in people of Turkish, Chinese and Filipino descent. The mutation is estimated to have arisen within the last 5,000 years.Free full text
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.Free full text

Protection against malaria

A number of studies have shown that the HbE mutation provides a degree of protection against infection with

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...

, in common with some other hemoglobinopathies. It is therefore probable that natural selection for the gene may explain why it is most prevalent in parts of the world where malaria has historically been

endemic Endemism is the state of a species being found only in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also foun ...

References

External links

Hemoglobin E fact sheet from the Washington State Department of Health

American Society of Hematology Educational Program profile of Hemoglobin E disorders

Orphanet Encyclopedia entry for Hemoglobin E

Hemoglobin E in Europeans
{{hemeproteins Hemoglobins