Research has suggested that screening for an inherited genetic defect known as familial hypercholesterolemia (FH) during routine immunization visits in early childhood could identify both children and parents at risk of premature coronary heart disease. This would be helpful as many people with this disorder are not diagnosed until they develop cardiovascular disease. The study was conducted in the United Kingdom and published in the New England Journal of Medicine.
FH is the most common inherited cause of early heart disease in people of European descent. In FH, a very high blood cholesterol level from birth leads to premature hardening of the arteries (atherosclerosis) and results in a 50% risk of having a heart attack by age 50 in men and at least a 30% risk by age 60 in women. Symptomless adults between ages 20 and 39 with FH have a 100-fold greater risk of a heart attack than others of the same age.
FH is caused by a dominant gene mutation inherited from one parent, so each of the couple's offspring has a 50% chance of being affected. The very rare inheritance of two copies of a mutation, one from each parent, causes heart disease in childhood, with death before age 30 if untreated. FH can be managed with lifestyle changes, such as diet and exercise, but typically requires treatment with lipid-lowering statins as well.
It is estimated that about 1 in 250 Americans carries an FH gene. In the U.S., there are no formal guidelines for FH screening. In its 2016 evidence report, the U.S. Preventive Services Task Force found that screening can identify children with FH and treatment is effective in lowering lipid levels in the short-term. Yet, it could not find any data from research studies on the long-term benefits or potential harms of lipid-lowering treatment in childhood or any evidence that screening for FH improves outcomes in adults. Further, routine lipid screening in children remains controversial. (Read Should All Children and Teens Be Screened For High Cholesterol?)
However, the Centers for Disease Control and Prevention recommend that healthcare practitioners follow the guidelines from the National Institute for Health and Care Excellence (NICE) in the UK for the diagnosis of FH in adults and children with elevated low-density lipoprotein cholesterol (LDL-C).
Following diagnosis, the NICE guidelines recommend that "cascade" testing with a combination of LDL-C measurement and DNA testing for genetic mutations be used to identify all relatives who are affected. These may include parents, siblings, children, aunts, uncles and grandparents (first and second degree relatives) as well as cousins, great-grandparents and great-grandchildren (third degree relatives), if possible. At present, family screening for FH is initiated when a person has premature coronary heart disease, especially when there is a family history.
The study in the UK looked at the feasibility of screening young children for both high cholesterol and the 48 most common gene mutations that cause FH. In 92 general medical practices, parents were offered heel stick 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.
Cholesterol was considered to be high if the level was greater than 99.9% of all the children's values. When cholesterol was elevated 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 an elevated cholesterol level in the first sample or if there were two elevated cholesterol values when no mutation had been identified. About one-third of the children with one of the 48 FH mutations did not have an elevated cholesterol level.
Screening was positive in 28 of the 10,118 children (0.3%), 20 with a known FH mutation. Of the 28 parents who tested positive for FH, 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 program for familial hypercholesterolemia 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." So far, there are no recommendations to screen all children in the U.S. for FH.