title: [LCAT deficiency: a nephrological diagnosis].
abstract: A genetic mendelian autosomal recessive condition of deficiency of lecithin- cholesterol acyltransferase (LCAT) can produce two different diseases: one highly interesting nephrologic picture of complete enzymatic deficiency (lecithin:cholesterol acyltransferase deficiency; OMIM ID #245900; FLD), characterized by the association of dyslipidemia, corneal opacities, anemia and progressive nephropathy; and a partial form (fish eye disease; OMIM ID #136120; FED) with dyslipidemia and progressive corneal opacities only. The diagnosis of FLD falls first of all under the competence of nephrologists, because end-stage renal disease appears to be its most severe outcome. The diagnostic suspicion is based on clinical signs (corneal opacities, more severe anemia than expected for the degree of chronic renal failure, progressive proteinuric nephropathy) combined with histology obtained by kidney biopsy (glomerulopathy evolving toward sclerosis with distinctive lipid deposition). However, the final diagnosis, starting with a finding of extremely low levels of HDL-cholesterol, requires collaboration with lipidology Centers that can perform sophisticated investigations unavailable in common laboratories. To be heterozygous for a mutation of the LCAT gene is one of the monogenic conditions underlying primary hypoalphalipoproteinemia (OMIM ID #604091). This disease, which is characterized by levels of HDL-cholesterol below the 5th percentile of those of the examined population (<28 mg/dL for Italians), has heritability estimates between 40% and 60% and is considered to be a predisposing condition for coronary artery disease. Nevertheless, some monogenic forms, and especially those associated with LCAT deficiency, seem to break the rule, confirming once more the value of a proper diagnosis before drawing prognostic conclusions from a laboratory marker. As in many other rare illnesses, trying to discover all the existing cases will contribute to allow studies broad enough to pave the way for further therapies, in this case also fostering the production by industries of the lacking enzyme by genetic engineering. Epidemiological studies, although done on selected populations such as hypoalphalipoproteinemia patients on dialysis and with the effective genetic tools of today, have been disappointing in elucidating the disease. Spreading the clinical knowledge of the disease and its diagnostic course among nephrologists seems to be the best choice, and this is the aim of our work.
authors.affiliation: SOC di Nefrologia e Dialisi, ASS2 Isontina Ospedale S. Giovanni di Dio, Gorizia, Italy. guiliano.boscutti@ass2.sanita.fvg.it
authors.forename: Giuliano
authors.initials: G
authors.lastname: Boscutti
authors.forename: Laura
authors.initials: L
authors.lastname: Calabresi
authors.forename: Stefano
authors.initials: S
authors.lastname: Pizzolitto
authors.forename: Emanuela
authors.initials: E
authors.lastname: Boer
authors.forename: Manuela
authors.initials: M
authors.lastname: Bosco
authors.forename: Piero Luigi
authors.initials: PL
authors.lastname: Mattei
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Martone
authors.forename: Neva
authors.initials: N
authors.lastname: Milutinovic
authors.forename: Dorina
authors.initials: D
authors.lastname: Berbecar
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Beltram
authors.forename: Guido
authors.initials: G
authors.lastname: Franceschini
mesh_terms: D000740:Anemia / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D008076:Cholesterol, HDL / Q000097:blood* / Q000378:metabolism; D003318:Corneal Opacity / Q000209:etiology; D003324:Coronary Artery Disease / Q000517:prevention & control; D018450:Disease Progression; D050171:Dyslipidemias / Q000209:etiology; D005818:Genetic Engineering; D006579:Heterozygote; D006801:Humans; D007558:Italy / Q000453:epidemiology; D007674:Kidney Diseases / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000473:pathology; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics*; D011507:Proteinuria / Q000209:etiology; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase