Facts Sheet
What is Sickle Cell Disease?
Sickle Cell Disease is a term qualifying a group of haematological genetic diseases that happen as a result of a mutation in a gene called the HBB gene. This gene encodes the beta chain in the haemoglobin molecule. Every individual has two distinct HBB genes, each inherited from a biological parent (i.e. one inherited from his father and the other inherited from his mother). These two genes each encode a beta haemoglobin chain. If both of an individual’s inherited HBB genes bear the mutation, both of his beta chains will be defective, resulting in Sickle Cell Disease.
If the individual inherited one mutated HBB gene from one parent, and one normal HBB gene from the other parent, then he doesn’t have the disease. He is only a carrier of the gene. Persons who carry one mutated HBB gene have a relative resistance to Falciparum malaria, are less likely to get malaria, run lower parasite counts when they do get malaria, and are less likely to die from malaria. It is postulated that this is what preserves the mutation. Children with Sickle Cell Disease usually have a short life expectancy and do not live long enough to pass the mutation on to their offspring. On the contrary, those with Sickle Cell traits are protected from malaria (which is a major killer disease in West African children) and hence live long enough to pass the mutation on to their offspring. This is why the mutation is sometimes referred to as a lethal advantage. This also explains why the mutation originated from Africa, which is a malaria endemic zone.
How is it inherited?
Sickle Cell is an autosomal recessive disease which means that it is inherited from parents who do not actually have the disease. The parents only have traits.
The inheritance of Sickle Cell Disease is not sex-linked. This means that the involved genes aren’t found on the X or Y Chromosomes. Both males and females can equally inherit the mutation from both of their parents. In parents who have one normal HBB gene and one mutated HBB gene, the normal gene produces normal haemoglobin (haemoglobin A) and this is enough to make them phenotypically healthy. Although they are clinically healthy, they still have the capacity to pass the mutated genes down to their children.
The mutated genes encode abnormal beta haemoglobin chains. Haemoglobin S is an example of a haemoglobin molecule with defective beta chains, so is Haemoglobin C. A normal HBB gene encodes normal beta haemoglobin chains. Haemoglobin A is a haemoglobin molecule with normal beta chains. Haemoglobin F is another type of haemoglobin molecule found in infants. It contains two gamma chains instead of two beta chains, and hence does not cause sickling, however its production is supressed after the individual is 6 months old.
Biological Mother is AS Biological Father is AS
- 25% chance in every pregnancy that their offspring will have haemoglobins S&S (Sickle Cell Disease)
- 50% chance in every pregnancy that their offspring will have haemoglobins A&S (Carriers of the mutated gene)
- 25% chance in every pregnancy that their offspring will have haemoglobins A&A (Normal)
Biological Mother is AS Biological Father is AC
- 25% chance in every pregnancy that their offspring will have haemoglobins S&C (Sickle Cell Disease)
- 25% chance in every pregnancy that their offspring will have haemoglobins A&S (Carriers of the mutated gene)
- 25% chance in every pregnancy that their offspring will have haemoglobins A&C (Carriers of the mutated gene)
- 25% chance in every pregnancy that their offspring will have haemoglobins A&A (Normal)
What is it called in our local dialects?
All ethnic groups in Ghana have a different name for Sickle Cell Disease. Here are some Sickle Cell Disease translations.
Language
- Ga
- Twi
- Ewe
- Fanti
- Hausa
Name
- Tswetsweetswee
- Ahotutuo
- Nududui
- Nwewee
- Amosani
Language
- Dagbani
- Wale
- Sisala
- Dagaari
- Nzema
Name
- Darimihi
- Gburigburihi
- Nakinchensi
- Korba baalun
- Nam sit amet
Epidemiology of Sickle Cell Disease in Ghana
What is the size of the problem?
In the absence of national level surveillance and newborn screening data and registry, the data and statistics on Sickle Cell Disease in Ghana may be an underestimation as the current figures only hold true for the section of the populace that have so far been screened for the mutation.
Over 300,000 babies are born with Sickle Cell Disease every year, this translates to more than 1000 babies being born with the disease every day.
- The frequency of AS is 20% in southern Ghana and 10% in Northern Ghana.
- The frequency of AC is 20% Northern Ghana and 10% Southern Ghana.
- More than 90% of Sickle Cell Disease cases are either SS or SC.
- The prevalence of Sickle Cell Disease is given as 2% of all newborns.
How does the disease present?
Although Sickle Cell Disease is a haemoglobinopathy, it affects multiple systems in the body. Haemoglobin is found within red blood cells. It binds to oxygen and transports oxygen around the body. The defective haemoglobin S or C produced when people have the disease cause the red blood cells they are found within to assume a sickle shape at low oxygen saturations. Unlike normal red blood cells that are pliant, sickle cells are rigid and break down easily after repeated sickling and unsickling episodes. Deoxygenated heamoglobin S is also less soluble than deoxygenated haemoglobin A, and tends to clump together and stick to the walls of blood vessels causing obstruction in small vessels and consequent reduced blood flow and reduced oxygen supply to various organs.
There are four major sickle cell crises.
Vaso-occlusive Crisis (VOC)
These are periodic episodes of pain which can last hours to days caused by inadequate oxygen delivery to organs. This may result in organ damage when it happens in the brain (stroke), the eyes (blindness), the kidneys (renal failure), the bones (avascular necrosis), the lungs (acute chest syndrome), penis (priapism) among others. VOC in the spleen causes splenic infarction causing a decline in the immune function of the spleen and increasing predisposition to infections. VOC is precipitated by infection, physical exertion, exposure to extremes of weather, fever, dehydration and psychological stress.
Aplastic Crisis
This is a temporary cessation of bone marrow activity affecting predominantly red cell precursors, triggered by parvovirus B19 (HPV B19) infection. The virus destroys the red cell precursors. This results in an acute and profound decrease in haemoglobin levels. Hb goes as low as 2 - 4g/dl necessitating hospital admission and blood transfusions. The bone marrow always recovers as the infection is transient and self-limiting.
Acute Haemolytic Crisis
Sickled red bloods cells break down 6 - 12 times faster than normal red blood cells do. The body is unable to produce enough red blood cells to replace the numbers being destroyed, resulting in severe anaemia. During acute hemolytic crisis, haemolysis occurs intravascularly (ie. within the blood stream) with evidence of hemoglobinemia (haemoglobin from the broken down red blood cells are released into the bloodstream) and hemoglobinurea (exess haemoglobin in the bloodstream is filtered in the kidneys, hence there are haemoglobin molecules in the urine), which results in renal damage and renal insufficiency.
Acute Splenic Sequestration Crisis (ASSC)
This is a sudden increase in spleen size associated with trapping of red cells. The spleen functions as the filter of the blood, clearing it of bacteria and abnormal cells. During an ASSC, blood flowing into the spleen for filtration does not flow out fast enough resulting in a large percentage of the body’s blood volume becoming acutely trapped within the spleen. It is characterised by an acute decrease in haemoglobin levels to 2-4g/dl and circulatory collapse, warranting an urgent blood transfusion. After two episodes of ASSC, the spleen will have to be taken out, leaving the patient vulnerable to multiple infections.
Stigmata of Sickle Cell Disease
What do people with severe expression of Sickle Cell Disease usually look like?
Smallish stature
People with Sickle Cell Disease have significantly lower weights, heights, sitting heights, mid arm circumferences, skin fold thickness and body mass indexes as compared to normal children with comparable sex and ages.
This is due to low bone mineral density.
Frontal bossing
Patients with Sickle Cell Disease tend to have unusually prominent foreheads.
This is because the frontal bone marrow mass expands due to the increased drive for erythropoeisis (since there is an increased need for more red blood cell production).
Gnatopathy
Gnatopathy is the protrusion of the upper teeth overriding the lower teeth with resultant depression of the nose.
This is often seen in people with Sickle Cell Disease because the maxillary bone marrow mass expands due to the increased drive for erythropoeisis (since there is an increased need for more red blood cell production).
Pallor
Sickle Cell patients are also chronically pale.
Since their red blood cells are breaking down faster than it should, their bodies are usually unable to produce enough red blood cells to replace the number being broken down, hence they are constantly in a haemoglobin deficit.
Jaundice
People with Sickle Cell Disease often have a yellowish discoloration of their eyes.
This is due to an increase in the amount of bilirubin (a yellow pigment) being produced due to the increased red blood cell break down (haemolysis).
Leg Ulcers
Chronic, painful, recurrent leg ulcers which take months – years to heal are common in people with Sickle Cell Disease. These are often seen around their ankles.
This is because the blood circulation in their legs isn’t optimal owing to episodes of micro-vascular occlusion.
People with Sickle Cell Disease are particularly susceptible to infections.
Children born with sickle cell disease develop functional asplenia in early childhood and are susceptible to overwhelming infection by encapsulated bacteria like Pneumococcus. Also, the necrotic tissues that remain after numerous infarctive episodes (vaso-occlusive crisis) become breeding grounds for microbes.
Commonest infections
Bacteria
- Streptococcus pneumoniae
- Hemophilus influenzae type B
- Salmonella species
- Staphylococcus aureus
- Escherichia coli and other gram-negative organisms
- Mycoplasma pneumoniae
- Chlamydia pneumoniae .
Viruses
- Human Parvovirus B19
- Hepatitis A, B, C
- Human Immunodeficiency Virus
Parasites
- Malaria
What are some common age-related complications of Sickle Cell Disease
Infancy and Childhood
- Sickle cell dactylitis
- Severe sepsis – pneumococcal, meningococcal and H influenzae
- Malaria
- Acute splenic sequestration syndrome
- Acute osteomyelitis – staphylococcal
- Strokes
- Enuresis
Adolescence
- Vaso – occlusive crises
- Priapism
- Leg ulcers
- Somatic growth retardation
- Psychosocial problems
- End – organ damage (Proliferative retinopathy, Avascular necrosis of femoral head, Gall stones, Impotence, Renal failure)
- Schooling problems (Absenteeism)
Adulthood
- Vaso – occlusive crises
- Chronic osteomyelitis
- Leg ulcers
- Gall stones
- Pregnancy related morbidity and mortality
- End – organ damage (Proliferative retinopathy, Avascular necrosis of femoral head, Gall stones, Impotence, Renal failure)
- Unemployment (Absenteeism)
What is the outcome of the disease in the developing world?
The prognosis of Sickle Cell Disease is variable and reflects the interaction between individual biology and environmental factors. There is 50-80% mortality in the population of children under 5 who have Sickle Cell Disease. Sickle Cell Disease is largely unrecognized, although it contributes up to 9-16% of under-5 mortality. In Ghana, Sickle Cell patients a have higher risk of dying from 3 of the top causes of under-5 mortality namely Pneumonia, Diarrhea & Malaria.
Those who make it beyond age 5 still have a short life expectancy of 30 years.
Decreasing under 5 mortality results in an epidemiologic shift, increasing the disease burden on the health system.
What are some of the factors influencing the outcome of the disease in Sickle Cell Patients?
The phenotyic expression of Sickle Cell Disease in many people is largely influenced by environmental factors. Certain enviromental inflences was increase or decrease the frequency of crises in these patients.
Patients who reside in the rural parts of Ghana unfortunately do not have ready access to the multidisciplinary specialized care required for Sickle Cell patients. The quality of medical care they have access to influences the phenotypic expression of the disease, causing more frequent crises.
Economic statuses and the level of illiteracy among individuals and families influence the quality of care they would be able to afford for their children who have Sickle Cell Disease. Optimal care translates to fewer crises.
In some instances medical facilities may have challenges providing blood for Sickle Cell patients due to blood bank shortage of blood. There are myths surrounding blood donation which generally make people apprehensive about donating blood. Other diagnostic facilities like the transcranial doppler ultrasnography that is requred to detemine a patients risk of developing a stroke may not be available in some hospitals.
Many parents may not know the statuses of their children or know much about the disease and may delay to seek medical help when their children start to show signs, symptoms and complications of the disease. Unfortunately, on some occasions, healthcare personnel advising these relatives may give inaccurate advice.
A patients living condition has been shown to have an influence on the disease outcome. Patients need to stay in well ventilated and warm and hygienic environments to avoid frequent crises.
How do people living with Sickle Cell Disease avoid crises?
Acute crises and their complications are the main causes of mortality in Sickle Cell patients.
There are a number of factors that trigger crises in Sickle Cell patients. Knowing and addressing and/or avoiding these will significantly reduce the number of crises they develop and give them better disease outcomes.
- Liberal oral fluid intake
- Wholesome nutrition
- Avoiding cold temperatures
- Antibiotic prophylaxis
- Vaccination against infections
- Daily folate supplementation
Is Sickle Cell Disease Treatable?
Medical advancements have brought more hope to people living with Sickle Cell Disease.
There are a number of interventions that boost red blood cell production, augment fetal haemoglobin production, and help mitigate the effects of the disease on the body.
Management
- Hydroxyurea
- Erythropoeitin
- Clotrimazole
- Chronic blood transfusion
Curative Treatment
Stem Cell Transplant
Stem cell transplant, has a success rate of 87%, and may potentially cure Sickle Cell disease. It involves replacing the abnormal stem cells residing in bone marrow with healthy cells from an eligible brother or sister.
Gene Therapy
The treatment uses a specially designed vector, a non-infectious lentivirus that contains genetic instructions to silence a gene called BCL11A. This BCL11A normally suppresses the production of fetal hemoglobin after birth, so silencing it allows healthy fetal hemoglobin to be made in red blood cells.
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