Deficit di lecitina:colesterolo aciltransferasi: dalla genetica alla terapia

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Pubblicato il 10 novembre 2016

Deficit di lecitina:colesterolo aciltransferasi, dalla genetica alla terapia

Lecithin:Cholesterol Acyltransferase Deficiency, from genes to therapy

Deficit di lecitina:colesterolo aciltransferasi, dalla genetica alla terapia

Lecithin:Cholesterol Acyltransferase Deficiency, from genes to therapy

Fabio Lucca¹, Alice Ossoli¹, Giuliano Boscutti², Guido Franceschini¹, Laura Calabresi¹

(1) Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano
(2) Nefrologia e Dialisi, Azienda Sanitaria Universitaria Integrata di Trieste

Corrispondenza a: Laura Calabresi; Centro E. Grossi Paoletti Dipartimento di Scienze Farmacologiche e Biomoleculari Università di Milano Via Balzaretti 9 20133 Milano Italy; Tel: +39 0250319906; Fax: +39 0250319900; E-mail: laura.calabresi@unimi.it

Abstract

L’enzima lecitina:colesterolo aciltransferasi (LCAT) è l’unico enzima nell’uomo in grado di esterificare il colesterolo nel plasma. Mutazioni a carico del gene che codifica per LCAT portano allo sviluppo di due distinte patologie: il deficit familiare di LCAT (FLD), in cui l’attività dell’enzima è totalmente assente, e il Fish-eye disease (FLD), in cui l’enzima mantiene parte della sua attività. I soggetti affetti da deficit di LCAT mostrano un profilo lipidico e lipoproteico caratteristico, con livelli di HDL-C mediamente ridotti, livelli di trigliceridi elevati e presenza in circolo di HDL piccole, discoidali e non mature chiamate preβ-HDL. Le manifestazioni cliniche del deficit di LCAT comprendono opacità corneale, che è peculiare e presente sia nei soggetti FLD che nei soggetti FED, anemia normocromica e danno renale. Il danno renale rappresenta la principale causa di morbidità e mortalità dei soggetti FLD. Attualmente non è ancora disponibile una terapia efficace per curare questa patologia e attualmente si ricorre nei casi più gravi a dialisi e trapianto renale.

Abstract

LCAT synthesizes most of the plasma cholesteryl esters, and plays a major role in HDL metabolism. Mutations in the LCAT gene cause two syndromes, familial LCAT deficiency (FLD) and fish-eye disease (FED), both characterized by severe alterations in plasma lipoprotein profile. Renal disease is the major cause of morbidity and mortality in FLD cases, but an established therapy is not currently available. The present therapy of LCAT deficiency is mainly aimed at correcting the dyslipidemia associated with the disease and at delaying evolution of chronic nephropathy. LCAT deficiency represents a candidate disease for enzyme replacement therapy. In vitro and in vivo studies proved the efficacy of recombinant human LCAT (rhLCAT) in correcting dyslipidemia, and rhLCAT is presently under development.

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Contenuti articolo

release 1
pubblicata il 10 novembre 2016
Da

Fabio Lucca¹, Alice Ossoli¹, Giuliano Boscutti², Guido Franceschini¹, Laura Calabresi¹

Parole chiave: lipoproteine

Key words: enzyme replacement therapy, high density lipoproteins, LCAT deficiency, Lecithin: cholesterol acyltransferase, lipoproteins

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Deficit di lecitina:colesterolo aciltransferasi: dalla genetica alla terapia

Deficit di lecitina:colesterolo aciltransferasi, dalla genetica alla terapia

Lecithin:Cholesterol Acyltransferase Deficiency, from genes to therapy

Deficit di lecitina:colesterolo aciltransferasi, dalla genetica alla terapia

Lecithin:Cholesterol Acyltransferase Deficiency, from genes to therapy

Abstract

Abstract

BibliografiaReferences

Contenuti articolo

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