Aortic and coronary atheromatosis in a woman with severe hypercholesterolaemia without LDL receptor alterations

C. R. Sirtori, A. L. Catapano, G. Franceschini, A. Corsini, G. Noseda, C. Fragiacomo, E. Panzeri, V. Vaccarino, S. Guenzi, G. Casari, F. Baralle

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)818-824
Number of pages7
JournalEuropean Heart Journal
Volume12
Issue number7
Publication statusPublished - 1991

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Keywords

  • apo B hypersynthesis
  • Coronary atheromatosis
  • Hypercholesterolaemia
  • LDL receptor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Sirtori, C. R., Catapano, A. L., Franceschini, G., Corsini, A., Noseda, G., Fragiacomo, C., Panzeri, E., Vaccarino, V., Guenzi, S., Casari, G., & Baralle, F. (1991). Aortic and coronary atheromatosis in a woman with severe hypercholesterolaemia without LDL receptor alterations. European Heart Journal, 12(7), 818-824.