Detection of familial hypercholesterolemia in a cohort of children with hypercholesterolemia: results of a family and DNA-based screening. 
The diagnosis of familial hypercholesterolemia (FH) in unselected children is difficult due to the frequent overlap of cholesterol values in affected and non-affected and the paucity of physical signs.  Nevertheless, detection and treatment of FH in childhood has been advocated to prevent atherosclerosis in these patients.  Here, we report the results of a screening program in a cohort of 157 unrelated, hypercholesterolemic (HC) children (age range 2-15 years; mean 8.3+/-3.4 years) carried out by a combination of family study and molecular analysis of the LDLR gene.  On the basis of the familial phenotype, 27 (17.2%) were classified as probable FH and 49 (31.2%) as affected by FCHL.  Among probable FH children, 14 (51.8%) carried mutant LDLR alleles, giving an overall 8.9% prevalence of FH.  Most of LDLR variants were already reported, but three new mutations G266C, T368M, and D451Y were identified.  Beside increased TC and LDL-C (p<0.001), FH children showed decreased HDL-C (p<0.05) and higher prevalence of family history of CAD when compared to non-FH children.  None presented tendon xanthomas.  We estimated that LDL-C >3.9 mmol/L was the best cut off value for diagnosing FH in these children, showing 79% sensitivity and 71.0% specificity.  We propose the use of a LDL-C cut off level associated with a family study to identify FH among HC children.