Sickle Cell Disease

INTRODUCTION
Sickle cell disease (SCD) is one of the most common genetic diseases worldwide and its highest prevalence occurs in Middle East, Mediterranean regions, Southeast Asia, and sub-Saharan Africa, especially, Nigeria. Sickle cell disease (SCD) is an umbrella term for a group of genetic disorders affecting the body’s red blood cells. It is the most prevalent genetic disease in the World Health Organization’s (WHO) African Region. About 5–7% of the global population carries an abnormal hemoglobin gene. The most predominant form of haemoglobinopathy ( Haemoglobin abnormality)  worldwide is sickle cell disease. The greatest burden of the disease lies in sub-Sahara Africa and Asia.

The prevalence of sickle cell trait (Genotype AS) ranges between 10 and 45% in various parts of sub-Saharan Africa .In Nigeria, carrier (Genotype AS) prevalence is about 20 to 30%, a ratio of 1-4 people are healthy carriers (Genotype AS) of the disease. SCD affects about 2 to 3% of the Nigerian population of more than 160 million .It is estimated that more than 300,000 babies are born with severe forms of haemoglobin abnormalities (haemoglobinopathies) worldwide each year.  75 percent of all patients with SCD live in Sub-Saharan Africa, Nigeria alone accounts for more than 100,000 new births of the sickle-cell disease. Nigeria has the highest burden of sickle cell disease in the world and is also the top sickle cell endemic country in Africa, with an annual infant death of about 150,000 representing more than 8% of infant mortality.  With advancement in medicine over the years, life expectancy of individuals with sickle cell disease has improved over the decades; a known sickle cell disease survivor will be 94 years old by 1st of November, 2019.

DEFINITION
Sickle cell disease is a group of inherited red blood cell (RBC) disorders that cause the production of abnormal hemoglobin (Hb). Haemoglobin is the oxygen- carrying component of the RBC. SCD is a chronic haemolytic disorder that is marked by tendency of haemoglobin molecules within red cells to polymerise and deform the red cell into a sickle (or crescent) shape resulting in characteristic vasoocclusive events and accelerated haemolysis. It is inherited in an autosomal recessive fashion either in the homozygous state (HB SS) or double heterozygous state ( e.g HB SC). When inherited in the homozygous state, it is termed sickle cell anaemia (SCA) which is the most common form of SCD. The red blood cells in individuals with sickle cell disease are shaped in sickles ( crescent shape) with jagged edges as opposed to  normal smooth ovals or discs shaped red blood cells . People with SCD have red blood cells that contain mostly haemoglobin S, an abnormal type of haemoglobin. SCD is typically a serious and lifelong condition, requiring long-term treatment and management.

Aetiopathogenesis (Causes) of Sickle Cell Disease
SCD is a qualitative haemoglobinopathy resulting from a structural change in the sequence of amino acids on the beta globin chain of the haemoglobin molecule due to a point mutation. The sickling mutation causes a single base change from adenine to thymine on the 17th nucleotide of the beta globin chain gene (HBB). This invariably translates into substitution of valine for glutamate on the 6th amino acid of the beta globin chain. The abnormal biochemistry of this mutant haemoglobin induces polymerization of Hb S molecules within the red cells, so called sickling. On the sickle haemoglobin, the glutamate protein molecule, which is hydrophilic, polar, and negatively charged, is replaced by a less polar, hydrophobic, neutral amino acid, valine. Under deoxy conditions (low oxygen), the abnormal valine residue causes intra-erythrocytic hydrophobic interaction of sickle haemoglobin

HOW IS SICKLE CELL DISEASE INHERITED?
If an individual inherits two hemoglobin S genes from their parents, that person may develop SCD. This may also be the case if an individual inherits one hemoglobin S gene plus another type of abnormal hemoglobin gene, such as thalassemia, hemoglobin C, hemoglobin D or hemoglobin E. If an individual inherits one hemoglobin S gene and one normal hemoglobin gene from their parents, they will have something known as sickle cell trait (Genotype AS) and become a carrier of sickle cell disease. People with sickle cell trait, however, will generally be healthy.

TYPES OF SICKLE CELL DISEASE
There are six main subtypes of sickle cell disease:
* HbSS (commonly known as sickle cell anemia)
* HbSC
* HbS beta-thalassemia
* HbSD
* HbSE
* HbSO
In all of these subtypes, “Hb” stands for “hemoglobin” (or referred to as genotype). All sickle cell diseases are hereditary hemoglobinopathies, which means that a person has inherited genetic deformations of hemoglobin from one or both parents. HbSS, or sickle cell anemia, is the most common subtype of sickle cell disease. In this subtype, the affected person inherits one sickle-cell gene from each parent. This is called a homozygous sickle cell disease.
In HbSC, the affected person inherits a sickle-cell gene from one parent and a gene for a defective form of hemoglobin (hemoglobin-C) from the other. HbS beta-thalassemia comes in two forms, beta 0-thalassemia, which is quite severe, and beta +-thalassemia, which is milder. These occur when the affected person has inherited a sickle-cell gene from one parent and a beta- thalassemia gene from the other.

HbSD, HbSE and HbSO are rarer subtypes of sickle disease. In these subtypes, the affected person has inherited a sickle-cell gene from one parent and a gene for a defective form of hemoglobin (Hemoglobin D, E or O) from the other. The severity of these subtypes varies. Individuals who have only inherited a sickle-cell gene from one parent and no abnormal genes from the other have what is known as sickle-cell trait.  In these cases, they are unaffected by the abnormal gene but may pass on a risk of sickle-cell disease to their children.  If two people with sickle-cell trait have children, those children have a one in four (1 in 4) chance of having sickle-cell disease, a one in four chance of being completely unaffected, and a one in two chance of being an unaffected carrier themselves.

To be continued in the next Edition.

 

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