Hemoglobin Disorder
There are various types of hemoglobins that differ from each other with respect to the structure of their globin chains. The haem moiety is identical in all types of hemoglobins. The α-globin chain consists of 141 amino acids, whereas, the βchain is composed of 146 amino acids. The hemoglobins consist of 2 α- and 2 non-α chains. Fetal hemoglobin (HbF) is the predominant hemoglobin in the intrauterine life. At birth 90% Hb is HbF. After birth HbF starts decreasing and is replaced with HbA and HbA2. When the infant is six months of age, it is about 5%. The adult level of 1% is reached at the end of the first year of life. In adults, hemoglobin consists of 97% HbA and 3% HbA2.
THE CLASSIFICATION OF HAEMOGLOBIN DISORDERS
- QUANTITATIVE DISORDERS OF HAEMOGLOBIN SYNTHESIS (THALASSAEMIA)
- QUALITATIVE OR STRUCTURAL DISORDERS OF THE HAEMOGLOBIN
Hemoglobin is the oxygen-carrying pigment of the red blood cells. It is a conjugated protein composed of four subunits. Each sub-unit is composed of a globin chain and a haem group. Each haem group has a single iron atom in the form of ferrous ion. When red blood cells pass through the lungs, they take up oxygen from the air, which combines with the ferrous iron of the haem. This reaction is not that of oxidation, but is of oxygenation i.e., the ferrous form of iron is not converted to the ferric form. Since there are four haem groups in one molecule of hemoglobin, it can combine with four oxygen molecules.
1. Quantitative Disorders - In these there is reduced synthesis of a structurally normal globin chain. These are called Thalassaemias and are named after the deficient globin chain. For example, in βThalassaemia, there is a reduced synthesis of the β globin chains.
2. Qualitative Disorders: In this category, the globin chain being synthesized is structurally abnormal. This is due to the substitution of one or more normal amino acids in any of the globin chains with different amino acids. In Sickle-Cell Anaemia, Valine substitutes Glutamic Acid at the sixth position of the β chain.
Thalassaemias are inherited, quantitative disorders of globin-chain synthesis. These are classified on the basis of the deficient or absent synthesis of the chains involved. The following are the main types of Thalassaemias:
1. α-thalassaemias: There is deficient or absent synthesis of α globin chains.
a. α-thalassaemia silent carrier state-(-α/ αα)
b. α-thalassaemia trait-(-α/-α or --/αα)
c. HbH disease (--/-α)
d. Hb Barts (hydrops foetalis syndrome)-(-/--)
2. β-thalassaemias: There is deficient or no synthesis of β globin chains.
a. β-thalassemia trait – (β+/o/ β)
b. β-thalassaemia major – (β+/o/ β+/o)
c. Thalassemia intermedia – (variable)
3. δβ-thalassemia: There is the deficient synthesis of both δ and β globin chains.
Structural disorders are further classified on the basis of the physical and chemical properties of an abnormal Hb molecule into:
1. Hemoglobins with altered solubility (HbS, C, etc.)
2. Unstable hemoglobins
3. Hemoglobins with altered oxygen affinity
4. Thalassaemic structural variants (Hb Lepore, HbE, Hb Constant Spring)
