A Blood Group That Should Not Be Possible
A district hospital types a newborn's blood as group O, Rh positive, during a workup for jaundice. The mother is group O and the father group AB, and their first child, now four years old, is group B. The laboratory repeats the test with two different antisera and gets the same result. The baby's red cells are not agglutinated by anti-A, anti-B or by the anti-H lectin from Ulex europaeus, whereas the father's cells are strongly agglutinated by anti-H. The mother's serum agglutinates reagent A and B cells; the father's serum agglutinates neither. The ward resident writes in the file that the result proves the baby was fathered by another man and plans to inform the family. The senior technician asks for saliva studies and molecular typing before anyone speaks to the parents, and also points out that the jaundice still needs its own explanation.
1. Using the parents' ABO genotypes, show why an O child is unexpected, and state whether non-paternity is the only explanation.
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Parental genotypes. The father is AB, so his genotype is IAIB; he forms IA and IB gametes in equal proportion. The mother is O, so her genotype is ii; all her gametes carry i.
Expected children. IA x i gives IAi (group A) and IB x i gives IBi (group B), each with a probability of one half. There is no way for this couple to produce an ii child, so a genuine group O child is not expected. The first child being group B is fully consistent and confirms that the father does transmit IB.
Is non-paternity the only explanation? No. Blood group phenotype is not determined by the ABO locus alone. The H gene (FUT1) is needed before A or B antigen can be built, and its product is the H antigen that anti-A and anti-B reagents indirectly depend on. A child who is homozygous recessive hh makes no H antigen, so any A or B allele inherited is silent and the cells react with neither anti-A, anti-B nor anti-H - they type as O. This baby could therefore be IB i hh: an apparent O group with a B allele present.
Conclusion. A single discrepant serological group is not proof of non-paternity. The absence of reaction with anti-H in the baby, while the father's cells react strongly, is the decisive clue and must be investigated before any allegation is made.
2. Explain the genetic interaction involved and give the expected proportions of blood groups among this couple's future children.
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The biochemical pathway. The H gene encodes a fucosyltransferase that adds a fucose residue to a precursor chain, producing the H antigen (the O antigen). The A allele adds N-acetylgalactosamine to H and the B allele adds galactose to H. Without H, there is nothing for the A or B enzymes to modify.
Type of interaction. This is recessive epistasis: a homozygous recessive genotype at the H locus (hh) masks the expression of the ABO locus, whichever alleles are present. The classical dihybrid F2 ratio for this kind of interaction is 12:3:1 instead of 9:3:3:1.
Applied to this family. For the baby to be hh, both parents must be carriers, so the father is IAIB Hh and the mother is ii Hh. The father gives IA or IB with probability one half each, and h with probability one half; the mother gives i and h with probability one half each.
- Bombay phenotype (hh, typed O): 1/2 x 1/2 = one quarter of children, irrespective of the ABO allele carried.
- Group A (IAi, H_): 1/2 x 3/4 = three eighths.
- Group B (IBi, H_): 1/2 x 3/4 = three eighths.
So the expected pattern in future children is 3/8 A, 3/8 B and 1/4 apparent O, and the first child being B is exactly what this predicts.
3. What clinical and communication decisions follow from this interpretation, including for the jaundice?
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Transfusion safety. A Bombay (Oh) individual carries naturally occurring anti-H in addition to anti-A and anti-B, so ordinary group O blood is dangerous. If transfusion is ever needed, only blood from another Oh donor (or the patient's own stored blood, or a rare-donor registry) is acceptable. The blood bank should flag the record permanently and the family should carry a card.
Confirmatory tests. Saliva testing for ABH substances, adsorption-elution to detect weak A or B antigen, and molecular typing of FUT1 (the H gene) and ABO. These settle the genotype rather than relying on serology alone.
Explaining the jaundice. ABO haemolytic disease of the newborn arises when a group O mother's IgG anti-A or anti-B crosses the placenta and attacks fetal cells carrying A or B antigen. This baby's cells carry no A, B or H antigen at all, so ABO incompatibility cannot explain the jaundice; look for physiological jaundice, G6PD deficiency, sepsis, or other causes, and treat on that basis.
Communication. The resident's draft note must be withdrawn. The correct message to the parents is that a rare inherited blood group pattern, not infidelity, explains the result - and that each future pregnancy carries a one-in-four chance of the same pattern.