RESUMO
BACKGROUND: Lipoprotein lipase (LPL) deficiency is a rare autosomal recessively inherited disease characterized by elevated triglyceride, low total cholesterol and quantitative and qualitative alterations of high-density lipoprotein (HDL). The aim of the present study was to explore HDL metabolic activities in a patient with LPL deficiency and in his family (n = 11). MATERIALS AND METHODS: Subjects were divided into four groups: proband (Ser447Stop/Arg170Leu carrier), Ser447Stop carriers, Arg170Leu carriers and silent mutation/wild-type carriers (controls). Cholesterol efflux from Fu5AH cells, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), paraoxonase 1 (PON1) and platelet-activating factor acetylhydrolase (PAF-AH) activities were evaluated. RESULTS: Comparison between the proband and the control group revealed that the boy had significantly reduced cholesterol efflux (P < 0.001), conserved LCAT activity (P > 0.05) and increased CETP activity (P < 0.001). As regards antioxidant enzymes, while PON1 activity was higher in the proband than in the controls (P < 0.0001), PAF-AH activity was reduced (P < 0.05). The other groups did not show relevant differences in comparison with controls. CONCLUSIONS: The presence of one mutation was not enough to introduce important modifications in HDL functions. Markedly reduced HDL levels can keep certain normal enzymatic activities, which probably tend to counteract the deleterious effects of LPL deficiency.
Assuntos
HDL-Colesterol/metabolismo , Lipase Lipoproteica/deficiência , Apolipoproteína A-I/metabolismo , Apolipoproteína A-II/metabolismo , Arildialquilfosfatase/metabolismo , Proteínas de Transporte/metabolismo , Pré-Escolar , Proteínas de Transferência de Ésteres de Colesterol , Feminino , Glicoproteínas/metabolismo , Heterozigoto , Humanos , Lipase Lipoproteica/genética , Masculino , LinhagemRESUMO
UNLABELLED: The case is reported of a 4-y-old boy with chylomicronaemia syndrome, under treatment with a low-fat diet and medium-chain triglycerides. The clinical and biochemical characteristics of the patient and 11 members of his family were studied. Lipoprotein profile, lipoprotein lipase (LPL) mass and activity were evaluated. Nucleotide substitutions in LPL promoter and exons were screened. The proband presented with severe hypertriglyceridaemia (triglycerides = 13.25 mmol l(-1)) and non-detectable LPL activity and mass. The boy was a compound heterozygote for four molecular defects in the LPL gene, two of which have not been reported before (CGT764 CTT/Arg170 --> Leu; GGA1482 --> GGT/Gly409 --> Gly). Among the family members, the proband was the only one who carried two genetic variants that modify LPL amino acid composition. CONCLUSION: The association of different alterations in the LPL gene could be a key factor in causing the severe phenotype observed. Moreover, treatment with a low-fat diet and medium-chain triglycerides failed to normalize the patient's hypertriglyceridaemia.