Anderson's disease: exclusion of apolipoprotein and intracellular lipid transport genes

Arterioscler Thromb Vasc Biol. 1999 Oct;19(10):2494-508. doi: 10.1161/01.atv.19.10.2494.

Abstract

Anderson's disease is a rare, hereditary hypocholesterolemic syndrome characterized by chronic diarrhea, steatorrhea, and failure to thrive associated with the absence of apo B48-containing lipoproteins. To further define the molecular basis of the disease, we studied 8 affected subjects in 7 unrelated families of North African origin after treatment with a low-fat diet. Lipid loading of intestinal biopsies persisted, but the pattern and extent of loading was variable among the patients. Electron microscopy showed lipoprotein-like particles in membrane-bound compartments, the densities (0.65 to 7.5 particles/mu(2)) and the mean diameters (169 to 580 nm) of which were, in general, significantly larger than in a normal fed subject (0.66 particles/mu(2), 209 nm mean diameter). There were also large lipid particles having diameters up to 7043 nm (average diameters from 368 to 2127 nm) that were not surrounded by a membrane. Rarely, lipoprotein-like particles 50 to 150 nm in diameter were observed in the intercellular spaces. Intestinal organ culture showed that apo B and apo AIV were synthesized with apparently normal molecular weights and that small amounts were secreted in lipid-bound forms (density <1.006 g/mL). Normal microsomal triglyceride transfer protein (MTP) and activity were also detected in intestinal biopsies. Segregation analyses of 4 families excluded, as a cause of the disease, significant regions of the genome surrounding the genes for apo AI, AIV, B, CI, CII, CIII, and E, as were the genes encoding 3 proteins involved in intracellular lipid transport, MTP, and fatty acid binding proteins 1 and 2. The results suggest that a factor other than apoproteins and MTP are important for human intestinal chylomicron assembly and secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Apolipoproteins A / biosynthesis
  • Apolipoproteins A / genetics
  • Apolipoproteins A / metabolism
  • Apolipoproteins B / biosynthesis
  • Apolipoproteins B / genetics
  • Apolipoproteins B / metabolism
  • Apolipoproteins C / biosynthesis
  • Apolipoproteins C / genetics
  • Apolipoproteins C / metabolism
  • Apolipoproteins E / biosynthesis
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Biopsy
  • Chromosomes, Human, Pair 4
  • Chylomicrons / metabolism
  • DNA, Satellite / analysis
  • Family Health*
  • Female
  • Genetic Linkage
  • Genotype
  • Heterozygote
  • Humans
  • Hypobetalipoproteinemias / genetics*
  • Hypobetalipoproteinemias / metabolism*
  • Hypobetalipoproteinemias / pathology
  • Intestinal Absorption / genetics
  • Intestinal Mucosa / metabolism
  • Intestines / pathology
  • Malabsorption Syndromes / genetics
  • Malabsorption Syndromes / metabolism
  • Malabsorption Syndromes / pathology
  • Male
  • Organ Culture Techniques
  • Pedigree
  • Polymorphism, Genetic
  • Triglycerides / biosynthesis
  • Triglycerides / metabolism*

Substances

  • Apolipoproteins A
  • Apolipoproteins B
  • Apolipoproteins C
  • Apolipoproteins E
  • Chylomicrons
  • DNA, Satellite
  • Triglycerides