Alterations in erythrocyte membrane lipid and fatty acid composition in Chediak-Higashi Syndrome

Chediak-Higashi syndrome (CHS) is an autosomal recessive disease characteri zed by the presence of abnormally large cytoplasmic organelles in all body granule producing cells. The molecular mechanism for this disease is still unknown. Functional disorders in membrane-related processes have been repor ted. Erythrocyte membranes from four CHS patients and 15 relatives includin g obligatory heterozygous were studied to examine potential alterations in the lipid and fatty acid profile of erythrocyte membranes associated with t his syndrome. Plasma concentrations of cholesterol, triglycerides, phosphol ipids, and apolipoproteins AI and B100, and the lipid components of very lo w-, intermediate- low- and high-density lipoproteins were also determined. CHS erythrocyte membranes were found to be enriched with lipids in relation to protein and to show: (1) an increase in cholesterol and choline-contain ing phospholipids (sphingomyelin and phosphatidylcholine) that predominate in the outer monolayer, which is higher than the increase in phosphatidylse rine and phosphatidylethanolamine, that are chiefly limited to the inner mo nolayer in normal red blood cells; (2) a relative palmitic acid and saturat ed fatty acid increase and arachidonic acid and unsaturated fatty acid decr ease, this resulting in a lower unsaturation index than controls. Changes i n CHS erythrocyte membrane lipids seem to be unrelated to serum lipid disor ders as plasma lipid and apolipoprotein concentrations were apparently in t he normal range, with the exception of a modest hypertriglyceridemia in pat ients and relatives and a decreased concentration of HDL cholesterol in pat ients. These findings indicate that CHS erythrocyte membranes contain an ab normal lipid matrix with which membrane proteins are defectively associated . The anomalous CHS membrane composition can be explained on the postulated effects of the CHS1/Lyst gene. (C) 2000 Elsevier Science B.V, All rights r eserved.