Alpha thalassaemia is the result of defective production of the alpha chain of haemoglobin. It is mainly found in the Far East, Middle East and Africa.
The normal alpha genotype is written alpha alpha/ alpha alpha as two alpha globin genes are inherited from each parent.
Unlike β thalassaemia where no-deletion mutations predominate, in α thalassaemia there is deletion of 1 or both a-globin genes from chromosome 16 (1).
- Deletion of one alpha globin genes of one of the chromosome pairs produces the haematologically silent carrier state - genotype - alpha/ alpha alpha.
- Deletion of two alpha globin genes produces the alpha thalassaemia trait. This is associated with mild hypochromic anaemia and may result from either
- loss of both pairs of genes from one chromosome - giving a --/alpha alpha genotype. This is most prevalent among Asians especially in S.E. Asia
- loss of one gene from each chromosome - giving a - alpha/- alpha genotype. This is most prevalent among black Africans.
- Deletion of three alpha globin genes results in Haemoglobin H disease with a genotype of --/- alpha. Alpha chain synthesis is severely suppressed so that unstable tetramers of excess beta globin - HbH - are formed. Clinically, it resembles beta thalassaemia intermedia.
- Deletion of all four alpha globin genes produces haemoglobin Bart's Hydrops syndromes - genotype --/--. It is incompatible with life, foetal death occurring at about 38 weeks
- The haplotype --/ (i.e. one chromosome pair having both alpha globin genes deleted) is known as alpha 0.
- The haplotype -alpha/ (i.e. one chromosome pair having a single alpha globin gene deleted) is known as alpha+
Reference:
- Piel FB, Weatherall DJ. The alpha-thalassemias. N Engl J Med. 2014 Nov 13;371(20):1908-16