title: Aortic and coronary atheromatosis in a woman with severe hypercholesterolaemia without LDL receptor alterations.
abstract: Familial hypercholesterolaemia (FH) is a monogenic disorder, with a strong family history, characterized by a deficiency in functional receptors for low density lipoproteins (LDL). The case of a patient with all the clinical traits of FH, including elevated cholesterol, xanthomas and early coronary and peripheral arterial lesions, but with a normal LDL receptor function, is described. In the patient the molecular weight and immunological properties of apolipoprotein (apo) B were normal; furthermore, autoantibodies to either LDL or to their receptor were also absent. The increased apo B/cholesterol ratio in LDL was compatible with the diagnosis of hyperapobetalipoproteinaemia. With the help of a turnover study using 131I homologous and 125I autologous LDL, it could be established that the patient had an almost three-fold increase in LDL-apo B biosynthesis, with, however, a fractional catabolic rate within normal limits. These findings pointed to the possibility of a genomic alteration in the region responsible for the control of apo B biosynthesis. However, extensive studies both at the cDNA level and in the 5' region of the apo B gene, failed to detect any significant alteration vs published nucleotide sequences. Although the exact mechanism for this unusual clinical presentation of an FH-like syndrome could not be uncovered, this case provides an extreme example of hypercholesterolaemia, with early and severe arterial disease, solely explained by an increased LDL biosynthesis.
authors.affiliation: Center E. Grossi Paoletti, University of Milano, Italy.
authors.forename: C R
authors.initials: CR
authors.lastname: Sirtori
authors.forename: A L
authors.initials: AL
authors.lastname: Catapano
authors.forename: G
authors.initials: G
authors.lastname: Franceschini
authors.forename: A
authors.initials: A
authors.lastname: Corsini
authors.forename: G
authors.initials: G
authors.lastname: Noseda
authors.forename: C
authors.initials: C
authors.lastname: Fragiacomo
authors.forename: E
authors.initials: E
authors.lastname: Panzeri
authors.forename: V
authors.initials: V
authors.lastname: Vaccarino
authors.forename: S
authors.initials: S
authors.lastname: Guenzi
authors.forename: G
authors.initials: G
authors.lastname: Casari
mesh_terms: D001018:Aortic Diseases / Q000209:etiology*; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology*; D001483:Base Sequence; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000209:etiology*; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011973:Receptors, LDL / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D011973:Receptors, LDL; D002784:Cholesterol