Sickle-cell disease shows autosomal recessive inheritance. Carriers, who are described as having the sickle- cell trait, are generally entirely healthy, although they can develop clinical problems, such as vaso-occlusive episodes (see below), in conditions of very low oxygen saturation such as may be encountered in deep-sea diving, ﬂying in unpressurized aircraft,
or during general anaesthesia (Ingram Vm 2002). The frequency of the sickle-cell trait is high in all populations originating from equatorial Africa, where carriers have a relative resistance to falciparum malaria.
Carrier frequencies as high as 20% have been found in countries such as Kenya and Uganda. Lower carrier frequencies of 5–10% are seen in the Middle East and in countries around the Mediterranean where malaria is endemic. The carrier frequency in African-Americans is approximately 8%, consistent with the incidence of homozygotes of 1 in 625.
The sickle hemoglobin (HbS) mutation confers a genetic advantage against malaria so carrier frequency is highest in areas where malaria is (or was) endemic, including;
- Mediterranean Europe
- The Middle East
- Some regions of India
- The Caribbean
- South and Central America
In these regions, the HbS gene frequency is 10-30%1. In Africa, about 200,000 new cases of sickle cell disease (SCD) occur each year. The incidence of SCD in other parts of the world is increasing due to population migration.
In the USA, SCD affects > 70,000 African-Americans and 1 in 375 newborns.5 In the UK, it affects 1 in 2,400 live births across ethnic groups, and > 12,000 individuals are living with SCD. This makes SCD the most common and fastest-growing genetic disorder in the UK.
PREVALENCE OF SICKLE CELL IN. NIGERIA
In 2006 the World Health Organisation (WHO) pronounced Nigeria as the country with the highest number of sufferers of sickle cell anaemia in the world. The global health watch dog puts the annual number of sickle cell anaemia suffers in Africa at about 200,000, noting that Nigeria accounts for 150,000 sickle cell anaemic children every year. Medical findings show that about 30 per cent of Nigerians are carriers of the mutant gene, with the prevalence rate at 20 per 1,000 births.
With the carrier frequency ranging between 20 per cent and 30 per cent of Nigeria's population, it means that more than 30 million Nigerians are carriers,'' the report stated (Hartwell et all 2000).
The disease, according to medical sciences, is inherited from both parents and is usually caused by some abnormalities in a type of haemoglobin called haemoglobin-s.
Symptoms of the disease vary, but a research conducted by (A. A. Adeyokunnu and R. G. Hendicks), both of the University College Hospital, Ibadan, shows that sufferers have painful episodes, usually referred to as crises which can last between hours and days.
Some carriers suffer abdominal pain, breathlessness, delayed growth and puberty, fatigue, fever, ulcers, among others,'' the report states. (Sen. GyangDantong), Chairman, Senate Committee on Health, notes that sickle cell anaemia has been proved to be more fatal than HIV and AIDS.
He describes the effects of the disease as very devastating, and declared that Nigeria could not afford to remain its world capital''. (Dr. Artemos Francis 2007), a Kaduna-based medical practitioner, believes that the first step toward checking the menace is to prevent its occurrence.
Sickle cell can only occur when two people, who carry the sickle cell trait, have a child together. We must intensify counselling intending couples to go for tests to determine their status.
Currently, some churches and mosques insist on the tests, but we have to step that up via legislations that would make it a compulsory state policy,'' he says. Francis also suggests steps to prevent the crises.
The sufferer must maintain good oxygen level to prevent dehydration. He or she must avoid strenuous activities, stress, smoking, high altitudes and too much sun exposure.''
Francis also suggests that a child with sickle cell anaemia should wear a Medic Alert Bracelet, while information on such children must be shared among teachers and other care givers.
He further suggests that sickle cell anaemia patients should join support groups where members share common experiences that could relieve stress. (Mrs. Mary Atanu), a Jos-based public health expert, shares Francis' suggestion that much attention be paid to the prevention of the disease. She explains that such is more helpful as the treatment for the ailment is usually very expensive.
All the treatment for sickle cell anaemia related complications are usually very costly; some complications require kidney transplant and gallbladder removal.
Other complications also require surgery for persistent painful erections, eye problems and ulcers.''(Odun Lade, 2005). She notes that bone marrow stem cell transplant can cure sickle cell anaemia, but points out that they are very expensive and out of reach of the poor.
Atanu notes that bone transplant abroad costs between N12 million to N15 million (WHO 1994). Marrow bone transplant was carried out last year on seven-year-old Matthew Ndik at the University of Benin Teaching Hospital (UBTH) at the cost of N5million The Federal Government has also expressed readiness to resuscitate the local production of Niprisan, the drug known for its universal efficacy in the management of sickle cell anaemia.
Health minister Prof. Onyebuchi Chukwu says “the stoppage of production of the drug created a huge vacuum in the management of sickle cell anaemia, and the resumption of production of the drug would restore hope for sickle cell sufferers''. (Prof. Kaniwen Gamaliel), Director-General, National Institute of Pharmaceutical Research and Development (NIPRD) agrees with the minister. “The resuscitation of the Niprisan project would rekindle hope to sickle cell patients, and I want to assure all Nigerians that we are fully committed to it,'' he assures. Medics and non-governmental organisations are of the view that public enlightenment should be intensified as sickle cell anaemia is avoidable. They also commended efforts made to reduce the pains of sufferers.
PATHOPHYSIOLOGY OF SICKLE CELL DISEASE on SICKLE CELL
Sickle-cell anaemia is caused by a point mutation in the β-globin chain of haemoglobin, causing the hydrophilic amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the sixth position. The β-globin gene is found on chromosome 11 (Lazarus, Hillard M, Schmaier, 2011). The association of two wild-type α-globin subunits with two mutant β-globin subunits forms haemoglobin S (HbS). Under low-oxygen conditions (being at high altitude, for example), the absence of a polar amino acid at position six of the β-globin chain promotes the non-covalent polymerisation (aggregation) of haemoglobin, which distorts red blood cells into a sickle shape and decreases their elasticity.
The loss of red blood cell elasticity is central to the pathophysiology of sickle-cell disease. Normal red blood cells are quite elastic, which allows the cells to deform to pass through capillaries. In sickle-cell disease, low-oxygen tension promotes red blood cell sickling and repeated episodes of sickling damage the cell membrane and decrease the cell's elasticity. These cells fail to return to normal shape when normal oxygen tension is restored. As a consequence, these rigid blood cells are unable to deform as they pass through narrow capillaries, leading to vessel occlusion and ischaemia.
The actual anaemia of the illness is caused by haemolysis, the destruction of the red cells, because of their misshape. Although the bone marrow attempts to compensate by creating new red cells, it does not match the rate of destruction (Alvin H et al 2010). Healthy red blood cells typically live 90–120 days, but sickle cells only survive 10–20 days. (Hillard M 2011).
Infants who receive 2 copies of the HbS mutation are homozygous (HbSS) and have the most severe disease phenotype. Heterozygous carriers (HbAS) have a mostly benign condition without clinical disability known as "sickle cell trait".
Although SCD is due to a single mutation, the disorders show considerable heterogeneity due to genetic and environmental factors