Premarital screening

What it is

Premarital screening is one of the points at which genetics acts as preventive medicine, beside neonatal screening on one side and prenatal prevention, antenatal diagnosis and preimplantation on the other. It is listed again among the preventative reproductive options as premarital genetic counselling and testing.

In this material premarital screening is premarital testing for hemoglobinopathies, and the test used is HPLC. Why it is done is stated where beta-thalassemia major is described: it is prevented by premarital screening. Prevention here means before the child, not before the disease in the person screened, and that is what makes the timing of the test the whole of its value.

Reading the HPLC result

What is asked is the reading of the result: given the HPLC values, which diagnosis, or which genotype, fits them.

HbA2 is what settles a beta thalassemia trait. An HbA2 above 3.5 is immediately beta thalassemia trait. So a premarital HPLC showing HbA 92%, HbF 1% and HbA2 5.2% is beta thalassemia trait, and not sickle cells anemia (HbSS), sickle cell trait (HbAS) or beta thalassemia major.

The second reading is a sickle one. An HPLC showing HbA 5%, HbA2 5.5%, HbF 12% and HbS 77.5% fits sickle cell S/B+ disease, and not sickle cell S carrier, sickle cell S/B0 disease or sickle cell S/S disease. The presence of some HbA at all is what rules out S/S and S/B0.

The third is the sickle carrier. A man who came with his fiancé for premarital testing, asymptomatic, with HbA 65.5%, HbA2 3.5, HbF 1% and HbS 30%, has HbAS sickle cell trait, and the rule given for that pattern is HbA above 50% with HbS below 40%.

Where a thalassemia is being confirmed rather than screened, hemoglobin electrophoresis confirms the diagnosis by identifying abnormal hemoglobin patterns, with beta-thalassemia typically showing increased levels of hemoglobin F and hemoglobin A2; the peripheral blood smear, iron studies to separate it from iron deficiency anemia, and genetic testing for mutations in the beta-globin gene complete the approach.