The hemoglobin types found in a normal adult are:
There are hundreds of mutations within the beta globin gene, but approximately 20 different alleles comprise 80% of the mutations found world wide. Within each geographic population there are unique mutations. Individuals who have beta thalassemia major are usually homozygous for one of the common mutations, or heterozygous for one of the common mutations and one of the geographically-unique mutations. Both lead to absence of beta globin chain production.
The beta thalassemia syndromes are much more diverse than the alpha thalassemia syndromes due to the diversity of the mutations that produce the defects in the beta globin gene. Unlike the deletions that constitute most of the alpha thalassemia syndromes, beta thalassemias are caused by mutations on chromosome 11 that affect all aspects of beta globin production: transcription, translation, and the stability of the beta globin product. Most hematologists feel there are three general categories of beta thalassemia: beta thalassemia trait, beta thalassemia intermedia and beta thalassemia major.
Splice site mutations also occur and are of clinical consequence, when combined with a thalassemia mutation. Three splice site mutations occur in exon 1 of the beta globin gene. These mutations result in three different abnormal hemoglobins: Malay, E, and Knossos. Hemoglobin E is a very common abnormal hemoglobin in the Southeast Asian population, and when paired with a b0 thalassemia mutation, can produce severe transfusion-dependent (Eb0) thalassemia. Hemoglobin E is described in the section on variant hemoglobins.
S, A, F
A, A2, C
A2, F
A, A2, F