Familial LCAT deficiency: from pathology to enzyme replacement therapy

Abstract Lecithin:cholesterol acyltransferase (LCAT) synthesizes most of the plasma cholesteryl esters, and plays a major role in HDL metabolism. Mutations in the LCAT gene cause two syndromes, familial LCAT deficiency and fish-eye disease, both characterized by severe alterations in plasma lipoprotein profile. Renal disease is the major cause of morbidity and mortality in familial LCAT deficiency cases, but an established therapy is not currently available. The present therapy of LCAT deficiency is mainly aimed at correcting the dyslipidemia associated with the disease and at delaying evolution of chronic nephropathy. LCAT deficiency represents a candidate disease for enzyme replacement therapy. In vitro and in vivo studies proved the efficacy of recombinant human LCAT in correcting dyslipidemia, and recombinant human LCAT is presently under development.