Congenital Disorders of Lipid Transport

Intestinal lipid absorption is orchestrated through the coordinated interactions of a number of gatekeeper genes, whose disruption or attenuated expression results in impaired lipid transport and accumulation of lipid droplets within enterocytes of the small intestine. Congenital disorders of lipid absorption are rare and virtually all the known causes are accounted for by mutations or deletions in the genes encoding microsomal triglyceride transfer protein (MTTP), apolipoprotein B (APOB), and Sar1-ADP Ribosylation factor, type B (SAR1B). Mutations or deletions in MTTP are responsible for abetalipoproteinemia (ABL). Mutations or deletions in APOB typically produce protein truncations, and function as autosomal-codominant alleles in familial hypobetalipoproteinemia (FHBL). Mutations or deletions in SAR1B manifest as autosomal-recessive alleles and give rise to chylomicron retention disease/Anderson’s disease (CRD). Mutations or deletions in diacylglycerol acyltransferase 1 have been described in association with impaired intestinal lipid absorption, leading to a rare congenital diarrheal disorder. Recognition and understanding of the underlying mechanisms of altered lipid transport in the background of mutations of these genes has led to the implementation of preventive strategies to attenuate the development of essential fatty acid and fat-soluble vitamin deficiencies, particularly vitamin A, D, E, and K.