title: Detection of familial hypercholesterolemia in a cohort of children with hypercholesterolemia: results of a family and DNA-based screening.
abstract: 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.
authors.affiliation: Department of Clinical and Applied Medical Therapy, Unit of Medical Therapy, University of Rome La Sapienza, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Campagna
authors.affiliation: Department of Paediatrics, University of Rome La Sapienza, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Martino
authors.affiliation: Department of Clinical and Applied Medical Therapy, Unit of Medical Therapy, University of Rome La Sapienza, Italy; Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Bifolco
authors.affiliation: Department of Clinical and Applied Medical Therapy, Unit of Medical Therapy, University of Rome La Sapienza, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Montali
authors.affiliation: Department of Paediatrics, University of Rome La Sapienza, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Martino
authors.affiliation: Department of Paediatrics, University of Rome La Sapienza, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Morrone
authors.affiliation: Department of Clinical and Applied Medical Therapy, Unit of Medical Therapy, University of Rome La Sapienza, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Antonini
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cantafora
authors.affiliation: Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Italy; Research Center for Clinical Trials (CRISC), University of Rome, La Sapienza.
authors.forename: Roberto
authors.initials: R
authors.lastname: Verna
authors.affiliation: Department of Clinical and Applied Medical Therapy, Unit of Medical Therapy, University of Rome La Sapienza, Italy; Research Center for Clinical Trials (CRISC), University of Rome, La Sapienza. Electronic address: marcelloarca@libero.it.
authors.forename: Marcello
authors.initials: M
authors.lastname: Arca
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D008078:Cholesterol, LDL / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005820:Genetic Testing; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000235:genetics; D007558:Italy; D008297:Male; D008403:Mass Screening; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics*; D012016:Reference Values
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D011973:Receptors, LDL