Anderson’s Disease

Abstract

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/ 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/ 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 Ͻ1.006 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.

Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk

“…It typically presents in infancy with failure to thrive in association with severe fat malabsorption (178)(179)(180)(181)(182)(183). Biochemically, CMRD is characterized by a selective absence of apoB48 in plasma, very low levels of total cholesterol, LDL-C, and HDL-C, plus substantially reduced apoB100 and A1 ( Table 4 ).…”

“…On the basis of structural ( 194,195 ), organ bath ( 187 ), histological ( 179 ), and of course, clinical data, the current thinking is that Sar1b is required to promote the transport of nascent chylomicrons out of the ER in specialized COPII-transport carriers. Moreover, CMRD patients homozygous for Sara2 null mutations (described in two families) may produce few, if any, of these putative specialized COPII-transport carriers, whereas patients with mutations affecting the GDP/GTP binding site of Sar1b (majority of affected families) may retain some ability to initiate the assembly of such carriers at the site of chylomicron production but not their fi ssion.…”

Low Rate of Production of Apolipoproteins B100 and AI in 2 Patients With Anderson Disease (Chylomicron Retention Disease)

“…7,16 After 2 years of a gluten-free diet, prescribed for a malabsorption syndrome with diarrhea, abdominal pain, and failure to thrive, a diagnosis of AD was made in January 1972 upon the typical clinical, biochemical, and ultrastructural findings because, he has adhered to a limited fat diet and has received vitamin E and A supplementation. Because of an allergic reaction, the vitamin supplementation was stopped in 2006.…”

A dynamic, cytoplasmic triacylglycerol pool in enterocytes revealed by ex vivo and in vivo coherent anti-Stokes Raman scattering imaging

“…Most current models of the synthesis of CMs show the resynthesized TG in this process entering the lumen of the endoplasmic reticulum (ER) where the assembly of CMs begins and do not highlight the potential for the resynthesized TG to enter a cytoplasmic TG storage pool unless there is a defect in CM synthesis or secretion (1,(3)(4)(5)(6)(7)(8). In fact, wild-type mice fed a high-fat diet, or challenged with an oil bolus by oral gavage, are commonly reported as having no lipid droplet (LD) accumulation in enterocytes (9)(10)(11).…”