RENAL DISEASE IN GENETIC LCAT DEFICIENCY: FROM PATHOGENESIS TO THERAPY

The lecithin: cholesterol acyltransferase (LCAT) enzyme is responsible for the esterification of all cholesterol in plasma. Defects in the gene coding for this protein cause the total or partial inability of the enzyme to esterify cholesterol, thus leading to two different syndromes: familial LCAT deficiency (FLD), and fish-eye disease (FED). While in normal subjects about 70% of plasma cholesterol is esterified, in subjects with LCAT gene mutations cholesterol is almost completely (FLD) or prevalently (FED) in the non esterified form, and tends to accumulate into tissues. Patients with both syndromes present with alterations in plasma lipid levels, with a marked reduction of HDL cholesterol (the good cholesterol). In addition, carriers of LCAT gene mutations, especially those with FLD, early develop severe renal disease, which frequently requires hemodialysis and may lead to renal transplantation. There is no cure for this disease, but available renal protection treatments may be useful to retard the development and progression of renal disease in high-risk carriers, once identified. The project presented to Telethon will help the understanding of the pathogenesis of the renal disease and will test the use of a recombinant form of the enzyme in preventing the renal damage in animal models of the disease.