Design: Prospective population screening programme with two-step biochemical then genetic testing, with bias adjustment by generalised linear mixed model
Population: 25,431 children aged 4.8-14.9 years screened at routine paediatric appointments in Bavaria from September 2020, via up to 480 paediatricians
Primary outcome: Detection of familial hypercholesterolaemia-causing variants and estimated population prevalence
Effect: 1,689 children had LDL cholesterol at or above 3.36 mmol/L; 17% of those genetically tested were positive, rising from 4.7% at 3.36-3.49 mmol/L to 78.6% above 5.17 mmol/L. Raw prevalence 1:90; adjusted for ascertainment bias 1:163, against gnomAD 1:165 and UK Biobank 1:176. Sequencing found 283 cases versus 157 by focused panel

The prevalence of familial hypercholesterolaemia is usually taught as about 1 in 250. VRONI tested that by screening children at routine paediatric appointments in Bavaria, using 0.2 mL of blood from a fingertip. Up to 480 paediatricians participated from September 2020, offering the test to children aged 4.8 to 14.9 years.

Of 25,431 children screened, 1,689 had LDL cholesterol at or above 3.36 mmol/L (130 mg/dL) — the 93rd percentile in this population — and went on to genetic testing. Seventeen per cent of those tested positive. The yield climbed steeply with the cholesterol: 4.7% at 3.36-3.49 mmol/L, rising to 78.6% above 5.17 mmol/L. Sequencing of the relevant genes outperformed a focused panel of the 48 commonest variants, finding 283 cases against 157.

The raw prevalence was 1 in 90, inflated by a founder LDLR variant present 40 times more often than the European average and by recruitment bias — practices that recruited fewer children found more cases. Adjusted, the estimate was 1 in 163, which lines up closely with gnomAD (1 in 165) and UK Biobank (1 in 176).

Two things follow for practice. The condition is roughly 50% commoner than the figure most clinicians carry, which changes the pre-test probability in any child with a raised cholesterol or a family history. And a two-step approach works: a cheap capillary lipid measurement selects who needs sequencing, and sequencing rather than a variant panel is what should follow.

Revise the working prevalence upward: about 1 in 160, not 1 in 250
Use a lipid measurement to select children for genetic testing, not the other way round
Where genetic testing is done, sequence the genes rather than screening a fixed variant panel
Interpret a child's LDL cholesterol against percentile, not adult thresholds
Note the local founder variant effect; prevalence varies by population and no Indian estimate is given here

Why it matters

The number clinicians carry for how common this is determines whether they investigate a raised cholesterol in a child at all.

The statistics, in plain English

The gap between the raw 1 in 90 and the adjusted 1 in 163 is the ascertainment bias the authors found and corrected for: practices that screened selectively found more cases, which inflates prevalence. That the adjusted figure matches two independent large genomic datasets is the strongest evidence that the correction was right. The 78.6% positive rate above 5.17 mmol/L is a positive predictive value in a screened population, not a probability that applies to a single child presenting with that value in a different setting.