Hemoglobinopathies / Sickle-cell anemia
Hemoglobin diseases or abnormalities can be either a defect in the rate of synthesis OR in the synthesis of abnormal hemoglobin which is the topic of this essay. This essay will outline the structural defects of hemoglobin S, hemoglobin C and hemoglobin E, the laboratory diagnosis and clinical aspects of the sickle cell disease will be mentioned as well. Finally, blood findings in sickle beta thalasemia combination will be described.
The structural defects of hemoglobin (HbS, HbC, and HbE) are usually due to point mutation in the beta globin gene.
*In HbE, there is a point mutation in the beta chain in position 26 of HbA that changes the sequence coding for glutamic amino acid to a sequence coding for the amino acid lysine.
*In HbC the genetic point mutation occurs in beta chain in position 6 of HbA leading to exchange of the amino acid glutamine to the amino acid lysine.
*The third type of haemoglobin structural defects, which will be described in more detail, is HbS. It occurs due to point mutation in beta chain of HbA in position 6 resulting in changing the sequence conding for glutamic acid to another coding for valine. Glutamic acid is an acidic amino acid, while valine is hydrophobic, this tells us that the new formed hemoglobin (HbS) is less soluble in cellular fluid than HbA (normal hemoglobin). As a result, HbS is going to precipitate leading to the formation of crystals giving the diseased red blood cells a sickle shape. Finally, cells become fragile and then lysis ensues. (1)
Sickle cell disease is an autosomal recessive i.e. subject can be trait (heterozygous) HbA/S and shows no clinical features. On the other hand, in homozygous individuals, several clinical features will appear. The degree of appearance of clinical features varies among different people. The most common clinical feature of sickle cell anemia is sickle cell crises: (2) (3)
1. Vaso-occlusive crises:
2. Hand & foot syndrome:
Seen in children in which 2 to 4 extremities are affected. Dorsa of the hands and feet are swollen and painful. Beside that, fever and leukocytosis may occur.
3. Visceral -sequestration crises:
4. Abdominal crises:
5. Bones & joints:
6. Hemolytic crises:
7. Infection crises:
Toxemia and heart failure occur more frequently in sicklers than in the general population (3)
Other clinical features:
(I) Lab. findings:
_Hemoglobin concentration is 6-9 g/dl, the average is 7.5 g/dl.
_Mean reticulocyte count: 8-12%
1. .Electrophoretic separation of hemoglobin. HbS is more predominant, while HbF found in varying concentrations. On the other hand, HbA2 concentration is normal, but there is no HbA.
2. Maneuvers. In this test hemoglobin is exposed to deoxygenated medium in which the HbS will change itís shape, while normal Hb will maintain itís structure.
3. Solubility test is the last test mentioned in this essay for the diagnosis of sickle cell disease. It is done as follows: blood is added to a buffered solution of a reducing agent. HbS precipitates making the solution looks turbid, where as blood free of HbS will show a clear solution.
RBCs show the morphological features of both HbS and thalasemia i.e. there are both sickle forms and red cells microcytosis, hypochromia, target cells and basophilic stippling.
To sum up, hemoglobinopathies can either be due to a defect in the function or the structure of hemoglobin. HbS, HbC and HbE are examples of structural defects of hemoglobin. Hemoglobin crises, such as, vaso-occlusive, hand & foot syndrome in children, abdominal crises, bone and joint crises and many other clinical features in addition to infections are some of the clinical problems that patients homozygous for the HbS gene may face. Moreover, the laboratory diagnosis of HbS disease can be done by electrophoresis, solubility test and deoxygenation test. Finally, a combination between HbS and beta thalasemia can exist in which the red blood cells show the morphological features of both HbS & thalasemia.
(1) licture by Dr. Gillite on molecular aspects of hemoglobinopathies.