Two AS Parents and an Uncertain Newborn Test
A couple, both 29, attend a genetic counselling clinic in Jamaica. Their 4-year-old son has had three painful crises and one episode of acute chest pain; haemoglobin electrophoresis showed HbSS. Both parents were screened during the mother's first pregnancy and each was HbAS. The mother is now 12 weeks pregnant. She is anxious because her son's newborn screening card was reported as 'HbF present, HbA not detected' and the result was not explained until he was 8 months old. The couple ask: what is the chance this baby will have sickle cell anaemia; and can a newborn screening result at birth be trusted to tell them whether the baby is affected? They also want to know whether the result would change if the baby needs a blood transfusion shortly after birth.
1. Use a genetic diagram to calculate the probability that the new baby will have sickle cell anaemia, and explain why the son is HbSS even though neither parent has the disease.
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Each parent is HbAS, so each can produce two types of gamete: A or S.
| A (father) | S (father) | |
|---|---|---|
| A (mother) | AA | AS |
| S (mother) | AS | SS |
The four equally likely outcomes are AA, AS, AS, and SS. Therefore the probability of a child with HbSS is 1 in 4, or 25% for each pregnancy. The probability of HbAS is 50%, and of HbAA is 25%.
The son is HbSS because he inherited an S allele from his mother and an S allele from his father. Each parent carries one normal A allele and one S allele, so neither parent has sickle cell anaemia; their red cells contain both normal and sickle haemoglobin. The son inherited the S allele from both sides, so he has no normal beta-globin allele to make HbA.
The 25% risk applies independently to this pregnancy. It is not changed by the fact that the first child is affected, and it does not mean that exactly one in four children in the family will be affected.
2. Evaluate the reliability of newborn screening for this family, including the effect of a blood transfusion. What should the clinic recommend?
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Newborn screening detects haemoglobin variants, usually by electrophoresis or high-performance liquid chromatography. At birth, HbF is still the main haemoglobin, so the report must be interpreted carefully. A baby with HbSS typically shows HbF and HbS, with no HbA. A baby with HbAS shows HbF, HbA, and HbS. The first son's report of 'HbF present, HbA not detected' was therefore abnormal and should have prompted urgent follow-up; it is consistent with HbSS or another beta-globin disorder, not with a normal result.
A blood transfusion can make the test unreliable. Donor red cells containing HbA can dilute the baby's own blood, so HbS may become undetectable or the pattern may look like HbAS or HbAA. The sample should ideally be taken before transfusion; if that is not possible, the result must be repeated after the transfused cells have cleared, often at 3 to 4 months or later.
The clinic should explain that newborn screening is a screening test, not a final diagnosis. It should recommend confirmatory testing, repeat testing after any transfusion, and prenatal diagnosis if the couple wish to know during this pregnancy. The counselling should be clear that a 'not detected' result after transfusion cannot rule out HbSS.