Sickle Cell and Thalassaemia (Haemoglobinopathies) are autosomal recessive inherited conditions that affect haemoglobin. Inheritance of one altered gene results in a healthy carrier.
If a couple are both carriers they have a 1 in 4 chance, in each pregnancy, of having an affected child, and a 2 in 4 chance of having a child who is a carrier.
The aim of the antenatal screening is to identify ‘at risk’ couples so that prenatal diagnosis may be offered before 12 weeks of pregnancy.
Sickle Cell Disease has a linked antenatal and newborn screening programme.
Sickle Cell
People with Sickle Cell Disease produce a structural variant of the haemoglobin protein (HbS). This affects the normal oxygen carrying capacity of red blood cells. When the cells are de-oxygenated and under stress in sickle cell conditions, they change shape from round flexible discs to elongated, or crescent moon shape.
These sickled cells cluster together and block blood vessels. This blockage prevents oxygenation of the tissues, resulting in pain from tissue hypoxia (sickle cell crisis), and also severe anaemia, susceptibility to infections, and damage to major organs such as the spleen.
Usually people with Sickle Cell Disease are homozygous for the HbS gene and produce only HbSS, but other haemoglobins in combination with HbS can sometimes cause a sickle cell disorder, for example HbSC, HbS/D.
There are approximately 240,000 healthy carriers and more than 12500 people affected with Sickle Cell in the UK. The prevalence is higher in some regions than others.
In high prevalence areas, all women are offered screening for sickle cell; in low prevalence areas, a family origin questionnaire is used to identify those women who should be offered screening for sickle cell disorders, due to the woman’s, or her partner’s, family origin.
Within the Northern Region, women living within the Newcastle area are deemed high prevalence; the rest of the Northern Region is deemed low prevalence.
Every year about 300 babies are born in England with sickle cell disorders (and 7000 healthy carriers). These babies are at high risk of death or complications, often arising from treatable infections in the first few years of life.
All newborn babies are screened for Sickle Cell. This negates any issues around ethnically ‘mixed’ couples. It also means that if the mother and father have not been tested that the condition can still be found in the newborn.
The aim of the newborn screening for sickle cell is to enable treatment with penicillin to be commenced immediately, prevenar vaccine to be given at 3 months of age, and so that parents can be educated about the management of the conditions.
If a newborn baby is shown to have a clinically significant haemoglobin variant, and the parents have not previously been tested, the parents should be offered sickle cell screening to assess the carrier status of both parents. Screening is carried out by the local haematology laboratories. Clinically significant variants include HbS, HbC, HbD, HbE, HbO Arab, and Hb Lepore.
Thalassaemias
Thalassaemia is the name given to a number of different inherited conditions that are due to an abnormality in the quantitative production of haemoglobin. Haemoglobin is made up of two alpha and two beta chains. If there is a problem with the alpha chains it is called alpha thalassaemia and if there is a problem with the beta chains it is called beta thalassaemia.
Beta thalassaemia major
Beta thalassaemia major is the result of haemoglobin with little or no beta chains. Problems occur postnatally. People with this will have a severe anaemia and they will need frequent blood transfusions which bring with it other problems with iron overload.
Alpha thalassaemia major
Alpha thalassaemia major is the result of haemoglobin chains that have no alpha chains. This is invariably fatal. An alternative name is Hb Bart’s hydrops fetalis.
Alpha or beta thalassaemia minor
Alpha or beta thalassaemia minor are both mild types of thalassaemia. People with these conditions have reduced amounts of either alpha or beta chains, but sufficient to make enough haemoglobin with the normal chains. They are carriers and may have mild anaemia.
If a baby has been affected by a major form of thalassaemia, the parents will need referral to a haematologist.
The analytical procedures used in newborn screening will detect Sickle Cell disease, beta thalassaemia and some other clinically benign haemoglobin variants. It will not detect beta-thalassaemia carriers. Parents may require genetic counselling to discuss options in future pregnancies.
Cascade testing for carrier status in other family members should be considered. Screening for haemoglobinopathies is carried out by the local haematology laboratory.