Hemoglobin E or haemoglobin E (HbE) is an abnormal hemoglobin with a single point mutation in the β 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 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. Also, this hemoglobin variant has a weak union between α and β globin, causing instability when there is a high amount of oxidant.^[1]

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 β 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.

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 β thalassemia.

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.

People who have hemoglobin E/β thalassemia have inherited one gene for hemoglobin E from one parent and one gene for β thalassemia from the other parent. Hemoglobin E/β thalassemia is a severe disease and it still has not got a universal cure. It affects more than a million people in the world^[2]. The consequences of hemoglobin E/β 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 α thalassemia. The presence of the α 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).^[3]

Hemoglobin E is most prevalent in Southeast Asia (Thailand, Myanmar, Cambodia, Laos, Vietnam^[4]), 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^[5]. 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.^[6][7]

• http://www.doh.wa.gov/ehsphl/phl/newborn/pubs/HBEFactSheet.pdf
• http://asheducationbook.hematologylibrary.org/content/2007/1/79.full
• http://www.orpha.net/data/patho/GB/uk-HbE.pdf
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1684388/pdf/ajhg00163-0214.pdf