Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevated serum of low-density lipoprotein cholesterol (LDL-C) and/or pathogenic variant in one of the FH-related genes1. Due to the cumulative exposure to elevated LDL-C levels from birth, individuals with FH are more likely to develop cardiovascular disease2. Half of the affected men and 30% of affected women will have a cardiovascular event before the age of 60 if not adequately treated3. The disease begins in childhood and progresses in varying degrees of severity depending on the number of cardiovascular risk factors. The frequency of heterozygous FH is estimated to be 1/250-1/500, making it possibly the most common life-threatening monogenic dominant disorder in humans4. The incidence of the severe homozygous course is 1:160,000-300,0005.

While in adults the serum LDL-C levels of FH patients and healthy individuals overlap, in children these two collectives are quite well separated by often lower LDL-C levels in healthy young individuals6. Leading criteria for diagnosis of FH in children are the determination of serum LDL-C levels and a history of cardiovascular risk factors in the family, e.g. an LDL-C ≥ 190 mg/dL (5 mmol/L) or an LDL-C ≥ 160 mg/dL (4 mmol/L) with family history of premature cardiovascular disease and/or high baseline cholesterol in one parent (phenotypic diagnosis). If a parent has a genetic defect, the LDL-C cut-off for the child is ≥ 130 mg/dL (3.5 mmol/L)7. In Germany, according to the national AWMF guidelines8, it is recommended that each child be offered a one-time determination of serum total cholesterol individually as part of a screening examination, either at preschool age or by age 11-12 years. Furthermore, in cases of known FH, screening should be selective and lipid determination should be offered at any age. There are no known data on the extent to which this strategy is used in Germany in reality. However, globally about 90% of adults and around 95% of children remain undiagnosed9. Up to now, there is only one 3-step universal FH screening program established for children10. In Slovenia, a total cholesterol (TC) screening at the primary pediatrician level is offered to all 5-year children as a part of a mandatory check-up, followed by LDL-C measurement in children with elevated TC levels and by genetic testing of the children with elevated LDL-C levels. Recently, the Prague Declaration called for action from national and European/international policy- and decision-makers addressing the outstanding barriers to the systematic implementation of FH pediatric screening across Europe.11

Within the framework of the Fr1dolin-Trial12, we evaluated the practicability of a new universal FH screening program by measuring directly the LDL-C serum levels in preschoolers.