RESUMO
BACKGROUND AND AIM: Familial hypercholesterolaemia is caused by variants in the low-density lipoprotein cholesterol metabolic pathway involving LDLR, APOB and PCSK9 genes. A national genetic testing service in Wales, UK has observed that no familial hypercholesterolaemia variant is found in almost 80% patients with the familial hypercholesterolaemia phenotype. It has recently been suggested that some adult patients with a familial hypercholesterolaemia phenotype may have cholesteryl ester storage disease which can also present as a mixed hyperlipidaemia. The commonest genetic cause of cholesteryl ester storage disease is an exon 8 splice junction variant in the LIPA gene (rs116928232, c.894G>A; E8SJM) previously found to have an allele frequency of 0.0011 (1 in 450 individuals) in a large European population. This study investigated the prevalence of the E8SJM in patients with a familial hypercholesterolaemia phenotype in Wales, UK. METHOD: A total of 1203 patients with a clinical suspicion of familial hypercholesterolaemia but no familial hypercholesterolaemia variant were invited to participate. Of these, 668 patients provided informed written consent. Stored DNA samples from 663 patients were genotyped for the E8SJM variant. RESULTS: Three heterozygotes were identified (allele frequency 0.0023). Whole gene sequencing of the LIPA gene was undertaken in these three individuals, but no other variants were found. Therefore, there were no cholesteryl ester storage disease patients (homozygote or compound heterozygote) identified in this cohort. CONCLUSION: The allele frequency 0.0023 (1 in 221 individuals) for the E8SJM variant was more prevalent in this cohort than in a European population study; however, no cholesteryl ester storage disease homozygotes were identified. We found no evidence to support routine testing for cholesteryl ester storage disease in adult patients with a familial hypercholesterolaemia phenotype.
Assuntos
Doença do Armazenamento de Colesterol Éster/epidemiologia , Hiperlipoproteinemia Tipo II/epidemiologia , Adulto , Idoso , Doença do Armazenamento de Colesterol Éster/genética , Estudos de Coortes , Heterozigoto , Homozigoto , Humanos , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo V/epidemiologia , Hiperlipoproteinemia Tipo V/genética , Masculino , Pessoa de Meia-Idade , Prevalência , Esterol Esterase/genética , País de Gales , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to assess retrospectively the prevalence and the predictive factors of acute pancreatitis (AP) in a population of patients referred in our endocrinology department for evaluation of very high triglyceride (TG) levels. METHODS: One hundred twenty-nine patients (119 with type IV phenotypes and 10 with type V phenotypes according to Fredrickson's classification) were referred to our hospital between 2000 and 2005. RESULTS: Twenty-six subjects (20.2% of the population) presented with AP. This population was significantly younger at diagnosis of hyperlipidemia (32 vs 40 years, P < 0.001) and at age of investigation (43 vs 48 years, P = 0.05) and had maximum TG levels greater than the population without AP (44.7 vs 24.5, P < 0.001). Subjects of the third tertile of TG levels had a 4.0-fold increased risk (95% confidence interval, 1.3-12.3) of AP compared with the first tertile. Severe pancreatitis (need for intensive care, C-reactive protein >150 mg/L, or Balthazar score >C) was observed in 71.5% of the patients. CONCLUSIONS: Twenty percent of patients with severe hypertriglyceridemia experience at least 1 attack of AP. Pancreatitis seems to occur in young patients at higher levels of TG than previously thought (85% of patients >30 g/L) and is associated with a severe clinical course.
Assuntos
Hiperlipoproteinemia Tipo IV/epidemiologia , Hiperlipoproteinemia Tipo V/epidemiologia , Pancreatite/epidemiologia , Doença Aguda , Adulto , Fatores Etários , Idade de Início , Estudos de Coortes , Feminino , Humanos , Hiperlipoproteinemia Tipo IV/complicações , Hiperlipoproteinemia Tipo V/complicações , Masculino , Pessoa de Meia-Idade , Pancreatite/etiologia , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de DoençaAssuntos
Doença das Coronárias/genética , Hiperlipoproteinemia Tipo IV/genética , Doença das Coronárias/epidemiologia , Suscetibilidade a Doenças , Humanos , Hiperlipidemia Familiar Combinada/epidemiologia , Hiperlipidemia Familiar Combinada/genética , Hiperlipoproteinemia Tipo IV/epidemiologia , Hiperlipoproteinemia Tipo V/epidemiologia , Hiperlipoproteinemia Tipo V/genética , Probabilidade , Fatores de RiscoRESUMO
Se presenta la historia de un caso de hiperlipoproteinemia tipo V en la infancia, primer reporte en Venezuela, diagnosticado desde los primeros días de vida. Después de descartadas todas las causas secundarias de esta enfermedad, se concluyó en un origen primario; fue imposible realizar estudio de la familia. El paciente ha presentado xantomas eruptivas, hepatoesplenomegalia, dolor abdominal que ameritó laparatomía exploradora, con extracción de líquido lechoso del abdomen; lipemia retinalis. Después de comenzado el tratamiento dietético específico para esta enfermedad se logró una disminución importante de los triglicéridos, aunque éstos se mantienen aún elevados. El paciente no ha presentado más complicaciones y se conserva asintomático con un crecimiento y desarrollo normal
