Lipid Profile Rather Than the LCAT Mutation Explains Renal Disease in Familial LCAT Deficiency
Por:
Lamiquiz-Moneo, I, Civeira, F, Gomez-Coronado, D, Blanco-Vaca, F, Villafuerte-Ledesma, HM, Gil, M, Amigo, N, Mateo-Gallego, R, Cenarro, A
Publicada:
1 nov 2019
Resumen:
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.
Filiaciones:
Lamiquiz-Moneo, I:
Hosp Univ Miguel Servet, CIBER Cardiovasc CIBERCV, Inst Invest Sanitaria Aragon IIS Aragon, Lipid Unit, Zaragoza 50009, Spain
Civeira, F:
Hosp Univ Miguel Servet, CIBER Cardiovasc CIBERCV, Inst Invest Sanitaria Aragon IIS Aragon, Lipid Unit, Zaragoza 50009, Spain
Univ Zaragoza, Dept Internal Med Psychiat & Dermatol, E-50009 Zaragoza, Spain
Gomez-Coronado, D:
Hosp Univ Ramon y Cajal, IRYCIS, CIBER Fisiopatol Obesidad & Nutr CIBEROBN, Dept Biochem Res, Madrid 28034, Spain
Blanco-Vaca, F:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, CIBER Diabet & Enfermedades Metab Asociadas CIBER, Serv Bioquim IIB St Pau,Dept Biochem & Mol Biol, Barcelona 08041, Spain
Villafuerte-Ledesma, HM:
Hosp Clin Univ Lozano Blesa, Nephrol Dept, IIS Aragon, Zaragoza 50009, Spain
Gil, M:
Biosfer Teslab SL, Reus 43201, Spain
Amigo, N:
Biosfer Teslab SL, Reus 43201, Spain
Univ Rovira & Virgili, IISPV, Metabol Platform, Madrid 43003, Spain
CIBER Diabet & Enfermedades Metab Asociadas CIBER, Madrid 28029, Spain
Mateo-Gallego, R:
Hosp Univ Miguel Servet, CIBER Cardiovasc CIBERCV, Inst Invest Sanitaria Aragon IIS Aragon, Lipid Unit, Zaragoza 50009, Spain
Univ Zaragoza, Dept Physiatry & Nursing, E-50009 Zaragoza, Spain
Cenarro, A:
Hosp Univ Miguel Servet, CIBER Cardiovasc CIBERCV, Inst Invest Sanitaria Aragon IIS Aragon, Lipid Unit, Zaragoza 50009, Spain
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