A 33-year-old man with nephrotic syndrome and lecithin-cholesterol acyltransferase (LCAT) deficiency. Description of two new mutations in the LCAT gene.

Familial lecithin–cholesterol acyltransferase (LCAT) deficiency is a rare autosomal recessive disease caused by mutation in the LCAT gene, located on chromosome 16q22 (GenBank accession nos: genomic DNA X04981, cDNA NM_000229). LCAT catalyses the formation of cholesteryl esters via the hydrolysis and transfer of sn-2 fatty acid from phosphatidylcholine to the 3-hydroxyl group of cholesterol. A deficiency of this enzyme leads to increased levels of phosphatidylcholine and unesterified cholesterol in the blood and to the formation of an abnormal lipoprotein (called ‘lipoprotein-X’) rich in both phosphatidylcholine and unesterified cholesterol. As a consequence, progressive lipid deposition occurs in various tissues, including the kidney [1], resulting in progressive glomerular sclerosis which becomes clinically manifest in the third to fourth decade of life and eventually leads to end-stage renal disease [2]. To date, 13 affected families have been found in Italy (including the one here described), but the disease may have been underdiagnosed. We here report on a 33-year-old man investigated for steroid-resistant nephrotic syndrome and progressive deterioration of renal function where clinical, morphological and biochemical data led to the diagnosis of familial LCAT deficiency, confirmed by the identification of two new mutations in the LCAT gene.