Two carriers in Bonaberi: counselling a family with sickle cell disease
A couple in Bonaberi have a three-year-old daughter with sickle cell anaemia. She has had three painful crises and one episode of severe anaemia that needed a blood transfusion. Both parents are healthy and have never been seriously ill. The mother is ten weeks pregnant. The husband's relatives blame the mother, say the family is cursed, and advise him to take a second wife who will 'give him strong children'. The husband asks the nurse whether the new baby will have the disease and whether anything could have been done to prevent it. Both parents agree to a blood test, which shows that they are both AS. The clinic has haemoglobin electrophoresis but no prenatal diagnostic service on site.
1. Using a genetic diagram, show the possible genotypes of the next child and state the probabilities. What is the probability that the next two children are both unaffected by sickle cell anaemia? (6 marks)
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Setting out the cross
Use HbA for the normal allele and HbS for the sickle allele. Each parent is AS and produces two kinds of gamete, A and S, in equal numbers.
| A (father) | S (father) | |
|---|---|---|
| A (mother) | AA | AS |
| S (mother) | AS | SS |
Probabilities for the next child
- AA, unaffected and not a carrier: 1 in 4 (25%)
- AS, unaffected carrier like the parents: 2 in 4 (50%)
- SS, sickle cell anaemia: 1 in 4 (25%)
So there is a 3 in 4 (75%) chance that the next child will not have the disease. Each pregnancy is an independent event, so the previous affected child does not change these odds.
Two children unaffected
Multiply the separate probabilities: 3/4 x 3/4 = 9/16, about 56%. Note carefully that 'unaffected' includes carriers; if the question had asked for two children who are neither affected nor carriers, that would be 1/4 x 1/4 = 1/16.
2. Explain why both parents are healthy although each carries the sickle allele, and why the allele is common in West and Central Africa. (5 marks)
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Why carriers are healthy
The allele carries a single base change (GAG to GTG) that replaces glutamic acid with valine at position 6 of the beta-globin chain. When oxygen is low, deoxygenated HbS molecules stick together and polymerise, distorting the red cell into a sickle shape. A carrier makes both HbA and HbS, with HbA in the majority. The presence of HbA interferes with polymerisation, so sickling only happens under severe stress such as extreme hypoxia, severe dehydration or very heavy exercise. Carriers are usually symptom-free and have a normal lifespan.
Why the allele persists
A child with SS has red cells that sickle even at moderate oxygen tension; these are destroyed by the spleen, causing anaemia, pain crises, and often death in early childhood without care. It would seem that natural selection should remove the allele, but it does not, because carriers have a real advantage: infection with the malaria parasite in AS cells leads to sickling and removal of the parasitised cells by the spleen, which limits how high the parasite load can rise. In malarial regions, carriers survive malaria better than AA people, so the allele is kept at a high frequency in the population. This is called balanced polymorphism. It is a biological fact, not a curse or a punishment.
3. Explain how you would counsel this couple. Include what the suggestion of a second wife would and would not change, and what can realistically be done for a child who is SS. (6 marks)
Read the worked answer
Correct the blame first
Explain calmly that both parents are carriers and that sickle cell disease is inherited, not caused by the mother and not a curse. Nothing either of them did during pregnancy caused it, and nothing could have prevented it after conception. The mother is at risk of being stigmatised by the family, and that must be challenged directly.
The second-wife suggestion
The risk depends on the genotype of the partner, not on which wife he chooses. If he takes a second wife who is AA, all her children will be carriers (AS) and none will have the disease, but they will all pass the allele on. If she is AS, the risk is again 1 in 4 for every pregnancy. So the answer is to test any partner, not to replace the mother. The existing daughter still needs her father.
What can be done
- Test the new baby after birth by haemoglobin electrophoresis, so that care starts early if the child is SS.
- For an SS child: penicillin prophylaxis and full vaccination, folic acid, plenty of fluids, prompt treatment of fever and infections, malaria prevention, avoidance of dehydration, cold and low oxygen, and early treatment of crises and acute chest syndrome. Transfusion and hydroxyurea where available; bone marrow transplant is the only cure and is rarely available.
- Prenatal diagnosis by chorionic villus sampling or amniocentesis with DNA testing is possible in principle but is not available at this clinic, and is expensive; discuss referral honestly rather than promising what cannot be delivered.
- The AS children in the family are healthy but need to know their status before they plan children, so that they can have their partners tested. Offer the couple ongoing follow-up and introduce them to a support group rather than leaving them with the numbers alone.