The primary problem appears to be a defect in cell
signaling and in mobilization of cellular lipids, leading to intracellular
cholesterol esters accumulation. This defect is compounded by a low plasma
concentration of apolipoprotein A-I (an essential component of HDL) caused
by a pathologically rapid catabolism. This results in a low level of HDL in
plasma, making it unable to scavenge cholesterol from tissues. Tissues that
accumulate excessive cholesterol include tonsils, liver, spleen, lymph
nodes, thymus, intestines, and peripheral nerves. Histology reveals deposits
of cholesterol esters outside of lysosomes in the cytoplasm.