Hemoglobin E

# Overview
Hemoglobin E or haemoglobin E (HbE) is an abnormal hemoglobin with a single point mutation in the  chain. At position 26 there is a change in the amino acid, from glutamic acid to lysine. HbE is one of the most common variant of normal hemoglobin. Hemoglobin E can be detected on electrophoresis. This hemoglobin variant is very common in Southeast Asia and it has a low frequency in black and white people.
The E mutation affects -gene expression creating an alternate splicing site in the mRNA at codons 25-27 of the -globin gene. Through this mechanism, there is a mild deficiency in normal  mRNA and production of small amounts of anomalous  mRNA. The reduced synthesis of  chain may cause  thalassemia. Also, this hemoglobin variant has a weak union between  and  globin, causing instability when there is a high amount of oxidant.

# Hemoglobin E disease (EE)
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 due to 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  thalassemia. People with hemoglobin E do not show any symptoms (there is usually no anemia or hemolysis). Subjects homozygous for the hemoglobin E allele have a mild hemolytic anemia and mild splenomegaly.

# Hemoglobin E trait: heterozygotes for HbE (AE)
Heterozygous AE occurs when the gene for haemoglobin E is inherited from one parent and the gene for haemoglobin 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 (MCV) and very abnormal red blood cells (target cells). Its clinical relevance is exclusively due to the potential for transmitting E or  thalassemia.

# Heterozygotes for HbE (SE)
Compound heterozygotes with hemoglobin sickle 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.

# Hemoglobin E/-thalassaemia
People who have hemoglobin E/ thalassemia have inherited one gene for hemoglobin E from one parent and one gene for  thalassemia from the other parent. Hemoglobin E/ thalassemia is a severe disease and it still has not got a universal cure. It affects more than a million people in the world. The consequences of hemoglobin E/ thalassemia when it is not treated can be heart failure, the enlargement of the liver, problems in the bones, etc.
There is a variety of genotypes depending on the interaction of HbE and  thalassemia. The presence of the  thalassemia reduces the among 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).

# Epidemiology
Hemoglobin E is most prevalent in Southeast Asia (Thailand, Myanmar, Cambodia, Laos, Vietnam), where its prevalence can reach 30 or 40%, and North-East India, where in certain areas carrier rates reach 60% of the population. In Thailand the mutation can reach 50 or 70%, and it is higher in the North-East of the country. It is also found in China, the Philippines, Turkey, Nepal, Sri Lanka, Pakistan, etc. The mutation is estimated to have arisen within the last 5,000 years. 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 E mutation.