|Hemoglobin E disease|
|Other names||Haemoglobin E|
|Crystal structure of Hemoglobin E mutant (Glu26Lys) PDB entry. Alpha chain in pink, beta chain in red. The lysine mutation highlighted as white spheres.|
Hemoglobin 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 (E26K). Hemoglobin E is very common among people of Southeast Asian, Northeast Indian, Sri Lankan and Bangladeshi 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. 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.
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 who are heterozygous for hemoglobin E (one normal allele and one abnormal allele) do not show any symptoms (there is usually no anemia or hemolysis). There are cases associated with haemolysis. Subjects homozygous for the hemoglobin E allele (two abnormal alleles) have a mild hemolytic anemia and mild enlargement of the spleen.
Heterozygous 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 (MCV) and very abnormal red blood cells (target cells), but clinical relevance is mainly 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 no universal cure. It affects more than a million people in the world. Symptoms of hemoglobin E/β-thalassemia vary but can include growth retardation, enlargement of the spleen (splenomegaly) and liver (hepatomegaly), jaundice, 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. 
There is a variety of phenotypes depending on the interaction of HbE and α-thalassemia. The presence of the α-thalassemia reduces the amount 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). This disease was first described by Virginia Minnich in 1954, who discovered a high prevalence of it in Thailand and initially referred to it as "Mediterranean Anaemia."
Hemoglobin E is most prevalent in mainland Southeast Asia (Thailand, Myanmar, Cambodia, Laos, Vietnam), Sri Lanka, Northeast India and Bangladesh. In mainland Southeast Asia, its prevalence can reach 30 or 40%, and Northeast India, 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 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. 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.