Research has suggested that screening for an inherited genetic defect known as familial hypercholesterolaemia (FH) during routine immunisation visits during early childhood could identify both children and parents at risk of premature coronary heart disease.
In FH a high blood cholesterol concentration from birth leads to premature atherosclerosis, and results in a 50% risk of having a heart attack by the age of 50 years in men and at least a 30% risk by 60 in women. Symptomless adults aged between 20 and 39 with FH have a 100-fold greater risk of a heart attack than others of the same age. A dominant gene is inherited from one parent, so each of the couple’s offspring has a 50% chance of being affected. The very rare inheritance of a mutation from each parent causes heart disease in childhood, with death before 30 if untreated.
It is estimated that about 1 in 500 of the UK population carries an FH gene. The National Institute for Health and Care Excellence (NICE) has given guidance about the diagnosis of FH in adults and children with raised low-density lipoprotein cholesterol (LDL-C) plasma concentrations. Following diagnosis, it recommends that ‘cascade’ testing with a combination of LDL-C measurement and DNA testing for genetic mutations is used to identify all first, second and, if possible, third degree relatives who are affected. At present family screening for FH is initiated when a patient has premature coronary heart disease, especially when there is a family history.
If FH is detected early, life-long treatment with statins can prevent premature disease. The population screening of young children and the parents of affected children has been proposed as a method for the pre-symptomatic identification of families. Researchers from Queen Mary University of London and Great Ormond Street Hospital have assessed the practicability of a child-parent approach in a Medical Research Council funded study that was published in The New England Journal of Medicine on 27 October 2016.
In 92 general medical practice surgeries, parents were offered heel prick blood tests for their one year old children at routine vaccination visits. During the three year study the offer was accepted by 11,101 parents (84%) and satisfactory blood samples were obtained from 10,118 children. The offer of screening did not reduce the proportion of parents who brought children for immunisation.
Cholesterol concentrations were measured in all children’s blood specimens and they were also examined by a quick test for 48 known FH mutations. Cholesterol was considered to be high if the concentration was greater than 99.9% of all the children’s values. When cholesterol was raised but no known mutation was found, mutations were sought by complex DNA sequencing. If none was found, the cholesterol measurement was repeated at least three months later. Screening was considered positive if there was both a mutation and a raised cholesterol concentration in the first sample or if there were two raised cholesterol values when no mutation had been identified. About one third of the children with one of the 48 FH mutations did not have a raised cholesterol concentration.
Screening was positive in 28 of the 10,118 children (0.3%), 20 with a known FH mutation. The researchers considered that the parent of each of the 28 children had a positive test whose blood sample either had the same mutation as the child or had the higher cholesterol concentration of the two parents. Of the 28 positive parents, 25 started treatment with statins (two who were pregnant planned to start later and one could not be contacted).
The researchers considered that they had shown the feasibility and efficacy of a child-parent screening programme for familial hypercholesterolaemia in general practice. They concluded that “it is a simple, practical and effective way of screening the population to identify and prevent a relatively common inherited cause of premature cardiovascular disease”.