Characterization of a new form of inherited hypercholesterolemia: Familial recessive hypercholesterolemia

G. Zuliani, M. Arca, A. Signore, G. Bader, S. Fazio, M. Chianelli, S. Bellosta, F. Campagna, A. Montali, M. Maioli, A. Pacifico, G. Ricci, Renato Fellin

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We previously described a Sardinian family in which the probands had a severe form of hypercholesterolemia, suggestive of familial hypercholesterolemia (FH). However, low density lipoprotein (LDL) receptor activity in fibroblasts from these subjects and LDL binding ability were normal. The characteristics of the pedigree were consistent with an autosomal recessive trait. Sitosterolemia and pseudohomozygous hyperlipidemia were ruled out. A second Sardinian kindred with similar characteristics was identified. Probands showed severe hypercholesterolemia, whereas their parents and grandparents were normolipidemic. FH, familial defective apoprotein (apo) B, sitosterolemia, and cholesteryl ester storage disease were excluded by in vitro studies. We addressed the metabolic basis of this inherited disorder by studying the in vivo metabolism of LDL in 3 probands from these 2 families. 125I-LDL turnover studies disclosed a marked reduction in the fractional catabolic rate (0.19 ± 0.01 versus 0.36±0.03 pools per day, respectively; P-1 d-1, respectively; P99mtechnetium-labeled LDL in the probands and compared them with those in normal controls and 1 FH homozygote. The probands showed a significant reduction in hepatic LDL uptake, similar to that observed in the FH homozygote. A reduced uptake of LDL by the kidney and spleen was also observed in all patients. Our findings suggest that this recessive form of hypercholesterolemia is due to a marked reduction of in vivo LDL catabolism. This appears to be caused by a selective reduction in hepatic LDL uptake. We propose that in this new lipid disorder, a recessive defect causes a selective impairment of LDL receptor function in the liver.

Original languageEnglish
Pages (from-to)802-809
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number3
Publication statusPublished - Mar 1999


  • apoB
  • Genetics
  • Hypercholesterolemia
  • LDL receptor
  • LDL turnover

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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