What are they?
Haemoglobin variants are abnormal forms of haemoglobin. Made up of haem, an iron-containing portion, and globin, amino acid chains that form a protein, haemoglobin (Hb or Hgb) molecules are found in all red blood cells. They bind oxygen in the lungs, carry the oxygen throughout the body, and release it to the body’s cells and tissues.
Normal haemoglobin types include:
- Hb A - makes up about 95%-98% of Hb found in adults); contains two alpha (α) protein chains and two beta (β) protein chains
- Hb A2 - makes up about 2%-3% of Hb; has two alpha (α) and two delta (δ) protein chains
- Hb F - makes up to 2% of Hb found in adults; has two alpha (α) and two gamma (γ) protein chains; the primary haemoglobin produced by the fetus during pregnancy; its production usually falls to a low level shortly after birth
Haemoglobin variants occur when genetic changes in the globin genes cause alterations in the amino acids that make up the globin protein. These changes may affect the structure of the haemoglobin, its behaviour, its production rate, and/or its stability. There are four genes that code for alpha globin chains and two genes that code for the beta globin chains. (For general information on genetic testing, see The Universe of Genetic Testing.) The most common alpha-chain-related condition is not an abnormality alpha thalassaemia, not strictly a “haemoglobinopathy” as it relates purely to underproduction of (normal) alpha chains, rather than “abnormal” haemoglobin constituents. The severity of alpha thalassaemia is governed by the number of genes affected. (See Thalassaemia for more information.)
Beta chain haemoglobin variants are inherited in an autosomal recessive fashion. This means that the person must have two altered gene copies, one from each parent, to have a haemoglobin variant-related disease. If one normal beta gene and one abnormal beta gene are inherited, the person is heterozygous for the abnormal haemoglobin, known as “carrier”. The abnormal gene can be passed on to any offspring, but it does not cause symptoms or health concerns in the carrier.
If two abnormal beta genes of the same type are inherited, the person is homozygous. The person would produce the associated haemoglobin variant and may have some associated symptoms and potential for complications. The severity of the condition depends on the genetic mutation and varies from person to person. A copy of the abnormal beta gene would be passed on to any offspring.
If two abnormal beta genes of different types are inherited, the person is “compound heterozygote”. The affected patient would typically have symptoms related to one or both of the haemoglobin variants that he or she produces. One or other of the abnormal beta genes would be passed on to each offspring.
Several hundred beta chain haemoglobin variants have been discovered; however, only a few are common and cause medical problems. They are discussed on the next page.