INTRODUCTION

Over 1000 different mutations of the globin chains of the human hemoglobin molecule have been discovered [1]. They are classified according to the type of mutation (eg, insertion, deletion, base change), the affected globin subunit (eg, alpha chain, beta chain), and by the clinical and hematologic phenotype (table 1 and table 2). This topic review will present an introduction to the most common of these mutations. Sickle hemoglobin and the thalassemias are discussed separately.

Laboratory and DNA-based methods for separation and detection of hemoglobin mutations are discussed separately. (See "Laboratory diagnosis of the hemoglobinopathies".)

INCIDENCE

It has been estimated that in excess of 300,000 children are born in the world each year with a severe inherited disorder of hemoglobin, and that approximately 80 percent of these births occur in low- or middle-income countries [2]. Accordingly, these disorders are presenting an increasing global health burden. (See "Community public health issues and the thalassemic syndromes: Lessons from other countries".)

The most important distinction that needs to be made when considering mutant hemoglobins is the frequency with which they are found in human populations. One group of mutant globin genes, including hemoglobins S, C, and E, is found at a frequency varying from 2 to 95 percent in different populations. These mutations are the product of expansion via selective external forces (eg, malaria) because, in the asymptomatic heterozygous form, they protect carriers from dying of malarial infection. These mutations are ethnic-specific, in that they are present in some human populations and not in others. (See "Protection against malaria in the hemoglobinopathies".)

Hemoglobin mutants in the second group exist at frequencies below 1 percent, and many times occur as spontaneous mutations in the propositus. These mutations usually have no medical consequences, but a subset can have serious abnormalities when present in the homozygous form. They are not ethnic-specific and examples of the same mutation, originating independently, can be found in any ethnic group.