Abstract

CARMO, Rute; CASTRO-FERREIRA, I  and  OLIVEIRA, João Paulo. Lecithin-cholesterol acyltransferase deficiency: a review for clinical nephrologists. Port J Nephrol Hypert [online]. 2017, vol.31, n.4, pp.286-292. ISSN 0872-0169.

Lecithin-cholesterol acyltransferase (LCAT) is the enzyme responsible for esterification of free cholesterol on the surface of lipoproteins, particularly in high-density lipoproteins (HDL), and is also involved in the reverse transport of cholesterol from peripheral tissues to the liver. LCAT is synthesized in the liver and circulates in plasma reversibly bound to lipoprotein particles, or in a lipid-free form. Primary LCAT deficiency is a rare inherited metabolic condition caused by homozygous or compound heterozygous mutation in the LCAT gene. It is associated with two distinct clinical syndromes, Familial LCAT Deficiency (FLD) and Fish-Eye Disease (FED), respectively caused by complete and partial deficiency of LCAT activity, but having in common markedly reduced plasma levels of HDL and apolipoprotein A-I. FLD is characterized by corneal opacities, haemolytic anaemia and chronic kidney disease (CKD), which may progress to end-stage renal disease (ESRD). The pathogenesis of FLD nephropathy is not clear, but accumulation of lipoprotein-X in the kidneys might be a major contributing factor. Corneal opacification is the only clinical hallmark of FED. In line with several reports of intermediate phenotypes, we have recently described an incomplete FLD phenotype in two Portuguese brothers, homozygous for a novel LCAT mutation, presenting with proteinuric CKD but no haemolytic anaemia, who developed noticeable corneal clouding only many years afterwards. Such a phenotype poses a diagnostic challenge to nephrologists, which will have to rely on accurate appraisal of the lipid profile abnormalities and a high index of suspicion to consider the right diagnosis. Further studies are needed to confirm whether recombinant human LCAT is effective in halting CKD progression in FLD patients. Meanwhile, renoprotective therapy by inhibition of renin-angiotensin-aldosterone system should be initiated as soon as possible. Despite early histological recurrence of the nephropathy in kidney grafts, renal transplantation remains a suitable therapy for FLD patients with ESRD

Keywords : Familial lecithin-cholesterol acyltransferase deficiency; Fish-eye disease; corneal clouding; chronic kidney disease; renal transplantation; recombinant human LCAT.

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