Familial hypobetalipoproteinemia in a hospital survey: Genetics, metabolism and non-alcoholic fatty liver disease

Carlos Gutiérrez-Cirlos, Mariá Luisa Ordóñez-Sánchez, María Teresa Tusié-Luna, Bruce W. Patterson, Gustav Schonfeld, Carlos A. Aguilar-Salinas

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12 Scopus citations


Introduction. Familial hypobetalipoproteinemia (FHBL) is an autosomal dominant disease characterized by abnormally low levels of apolipoprotein-B (apoB) containing lipoproteins. FHBL is caused by APOB, PCSK9 or ANGPTL3 mutations or is associated with loci located in chromosomes 10 and 3p21. However, other genes should be involved. This study describes the kinetic parameters of the apoB containing lipoproteins and sequence abnormalities of the APOB and PCSK9 genes of FHBL patients identified in a large hospital based survey. Material and methods. Cases with primary or secondary causes of hypobetalipoproteinemia were identified. ApoB kinetics were measured in cases with primary forms in whom truncated forms of apoB were not present in VLDL (n = 4). A primed constant infusion of [13C] leucine was administered, VLDL and LDL apoB production and catabolic rates measured by a multicompartmental model and compared to nor-molipemic controls. In addition, these subjects had an abdominal ultrasound and direct sequencing was carried out for the PCSK9 and apoB genes. Results. Three individuals had normal apoB production with increased catabolic rate; the remaining had reduced synthetic and catabolic rates. Various polymorphisms, some of them previously unreported (*), in the PCSK9 gene (R46L, A53V, I474V, D480N*, E498K*) and in the apoB gene (N441D*, Y1395C, P2712L, D2285E*, I2286V, T3540S*, T3799M*) were found in the FHBL patients. We found hepatic ultrasound changes of hepatic steatosis in only one of the four probands. Conclusion. FHBL without truncated apoB is a heterogeneous disease from a metabolic and a genetic perspective. Hypobetalipoproteinemia is a risk factor but not an obligate cause of steatosis.

Original languageEnglish
Pages (from-to)155-164
Number of pages10
JournalAnnals of Hepatology
Issue number2
StatePublished - 2011


  • ApoB-100 kinetics and metabolism
  • Hepatic steatosis
  • Hypocholesterolemia
  • Proprotein convertase subtilisin/kexin type 9


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