Renal complications are the major cause of morbidity and mortality in patients with familial
lecithin-cholesterol acyltransferase (
LCAT) deficiency (FLD). We report three FLD patients, two of them siblings-only one of whom developed renal disease-and the third case being a young man with early renal disease. The aim of this study was to analyze the clinical characteristics and possible mechanisms associated with renal disease in these patients. Plasma
lipid levels, LCAT activity,
lipoprotein particle profile by NMR and FPLC, free and esterified
cholesterol, presence of
lipoprotein X (LpX) and
DNA sequencing in the three FLD patients have been determined. The three cases presented clinical characteristics of FLD, although only one of the siblings developed renal disease, at 45 years of age, while the other patient developed the disease in his youth. Genetic analysis revealed new missense homozygous mutations, p.(Ile202Thr) in both siblings and p.(Arg171Glu) in the other patient.
Lipoprotein particle analysis showed that the two patients with renal disease presented higher numbers of small
very low-density lipoprotein (VLDL) and a higher concentration of
triglycerides in VLDL. This study reports three new cases of
LCAT deficiency, not previously described. Renal disease is not only dependent on
LCAT deficiency, and could be due to the presence of VLDL particles, which are rich in
triglycerides, free
cholesterol and LpX.