familial hypobetalipoproteinaemia

Last reviewed 03/2021

• primary hypobetalipoproteinemia (HBL) includes a group of genetic disorders:
  • abetalipoproteinemia (ABL) and chylomicron retention disease (CRD)
    • ABL and CRD both have a recessive transmission
  • familial hypobetalipoproteinemia (FHBL) with a co-dominant transmission
• ABL and CRD are rare disorders due to mutations in the MTP and SARA2 genes, respectively
  • chylomicron retention disease (CRD)
    • absence of apoB-48-containing lipoproteins
    • affected individuals do not have chylomicrons in plasma following a fat containing meal, and have a marked accumulation of lipids in enterocytes
      • hepatic apoB synthesis is maintained and so low density lipoproteins are present in the plasma
    • clinical characteristics
      • steatorrhea, growth retardation, malnutrition, accumulation of lipid droplets in enterocytes
• heterozygous familial hypobetalipoproteinemia (FHBL) is much more frequent than ABL or CRD
  • FHBL subjects often have fatty liver and, less frequently, intestinal fat malabsorption
  • FHBL may be linked or not to the APOB gene
    • most mutations in APOB gene cause the formation of truncated forms of apoB - these forms of apoB may or may be not secreted into the plasma
      • truncated apoBs with a size below that of apoB-30 are not detectable in plasma (more frequent in patients with the most severe phenotype)
        • heterozygotes of FHBL linked to apoB gene: asymptomatic, fatty liver, loose stools, mild fat malabsorption, gallstones
        • homozygotes/compound heterozygotes of FHBL linked to apoB gene: fatty liver, steatorrhea, acantocytosis, neurological abnormalities
        • apoB or LDL levels compared with controls - reduced < 30%
      • approximately 50% of FHBL subjects are carriers of pathogenic mutations in APOB gene
        • thus a large proportion of FHBL subjects have no apoB gene mutations or are carriers of rare amino acid substitutions in apoB with unknown effect

Reference:

• (1) Schonfeld G. Familial hypobetalipoproteinemia: a review. J Lipid Res 2003;44: 878-883.