title: Plasma non-cholesterol sterols: a useful diagnostic tool in pediatric hypercholesterolemia.
abstract: Current guidelines strongly recommend the identification of genetic forms of hypercholesterolemia (HC) during childhood.The usefulness of non-cholesterol sterols (NCS) in the diagnosis of genetic HC has not been fully explored. Plasma NCS were measured by gas chromatography/mass spectrometry (GC/MS) in 113 children with hypercholesterolemia affected by: autosomal dominant hypercholesterolemia (ADH), familial combined hyperlipidemia(FCHL), polygenic hypercholesterolemia (PHC), and in 79 controls to evaluate: i) plasma NCS profile in different genetic HC and ii) the usefulness of NCS for the diagnosis of HC beyond current clinical criteria. ADH was characterized by raised lathosterol/total cholesterol (TC) and reduced phytosterols/TC ratios, indicative of increased cholesterol synthesis. FCHL showed a slight increase of lathosterol/TC ratio, whereas PHC showed increased phytosterols/TC ratios, indicative of increased cholesterol absorption. In a post hoc discriminant analysis of patients with HC, lipid values correctly classified the 73% (14 of 19) of ADH, whereas the inclusion of plasma sterols allowed the correct identification of all 19 patients with ADH. FCHL was not differentiated from PHC (62 versus 69%).In conclusion, NCS measurement showed that cholesterol plasma levels are related to the cholesterol synthesis in ADH and to cholesterol absorption in PHC. NCS improve the detection of ADH in pediatric patients, whereas FCHL diagnosis is not improved.
authors.affiliation: Department of Clinical Medicine and Emerging Diseases, University of Palermo, Palermo I90127, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Noto
authors.forename: Angelo B
authors.initials: AB
authors.lastname: Cefalù
authors.forename: Giacoma
authors.initials: G
authors.lastname: Barraco
authors.forename: Eliana
authors.initials: E
authors.lastname: Martino
authors.forename: Francesca
authors.initials: F
authors.lastname: Fayer
authors.forename: Mariangela
authors.initials: M
authors.lastname: Minà
authors.forename: Anna
authors.initials: A
authors.lastname: Montali
authors.forename: Marcello
authors.initials: M
authors.lastname: Arca
authors.forename: Maurizio
authors.initials: M
authors.lastname: Averna
authors.forename: Francesco
authors.initials: F
authors.lastname: Martino
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002784:Cholesterol / Q000031:analogs & derivatives / Q000097:blood; D016002:Discriminant Analysis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D020022:Genetic Predisposition to Disease; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D007558:Italy; D008297:Male; D020412:Multifactorial Inheritance; D010840:Phytosterols / Q000097:blood; D011237:Predictive Value of Tests; D012855:Sitosterols / Q000097:blood; D013261:Sterols / Q000097:blood*
chemical_list: D015415:Biomarkers; D010840:Phytosterols; D012855:Sitosterols; D013261:Sterols; C021273:campesterol; C025473:gamma-sitosterol; C001521:lathosterol; D002784:Cholesterol