Rising cholesterol levels in children with familial hypercholesterolaemia

Reference ranges (5th to 95th percentile) for fasting total serum cholesterol concentration were calculated for 571 unrelated children aged 4-19 years, without known predisposition to hypercholesterolaemia. Values were 3.31-5.81 mmol.l-1 for boys and 3.20-5.66 mmol.l-1 for girls, without significant differences between sexes at any age, compared to our laboratory reference ranges for men (3.46-6.87 mmol.l-1) and women (3.00-6.38 mmol.l-1). A further 85 children, each with a first degree relative with Familial Hypercholesterolaemia (FH), were studied. Initially, 39 had high cholesterol concentrations suggestive of FH. Repeated serial measurements were carried out in 18 of the 46 apparently unaffected children. Seven of these showed marked increases in serum cholesterol over 1-7 years, reaching concentrations above the 95th centiles of the appropriate reference ranges. The annual rate of increase was significantly higher than in the 11 who remained normocholesterolaemic. In 3 of these 7 children, diagnosis of FH was confirmed retrospectively, using recombinant DNA technology to show that each had inherited the defective allele of the LDL-receptor gene from an affected parent. Thus, serial cholesterol measurements may be needed to confirm or exclude FH in potential heterozygotes, while DNA studies can be used for definitive diagnosis in some families.