Browsing by Author "Guerra, A."
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- Caracterização bioquímica e molecular de doentes com diagnóstico clínico de Dislipidemia Familiar CombinadaPublication . Santos, T.; Rato, Q.; Gaspar, I.M.; Guerra, A.; Rico, M.T.; Sequeira, S.; Silva, J.M.; Bourbon, M.A Dislipidemia Familiar Combinada (FCHL) é uma doença poligénica caracterizada por hiperlipidemia simples ou combinada, variabilidade intra-individual e intra-familiar do perfil lipídico, ApoB elevada (> 120 mg/dL) e risco elevado de doença cardiovascular (DCV). A sua causa é desconhecida mas alterações nos genes LPL, APOAIV, APOAV, APOCIII e USF1 parecem contribuir para o seu fenótipo. O objectivo deste estudo é caracterizar bioquímica e molecularmente doentes com diagnóstico clínico de FCHL. Todos os exões e promotor dos genes LPL, APOAIV, APOAV, APOCIII e regiões do gene USF1 (s1,s2) de 41 doentes foram amplificados por PCR e sequenciados. O colesterol total (CT), c-LDL, c-HDL, sdLDL, trigliceridos (TG), apoB e apoCIII foram determinados num aparelho automatizado. Em alguns doentes as sdLDL foram também analisadas por electroforese de lipoproteínas. A ApoAIV e ApoAV foram quantificadas por ELISA. Foram encontradas alterações genéticas em 37 doentes, 3 não descritas (APOAIV Q359_E362, APOAV D332fsX336 e APOCIII 3269C>A). O índex com a alteração Q359_E362del apresentou valores normais de apo AIV (15.5 mg/dL) e o índex com a alteração D332fsX336 apresentou valores baixos de apo AV (74.5 ng/mL). Os doentes estudados apresentam valores elevados de CT (285 ± 83 mg/dL), c-LDL (189 ± 85 mg/dL), TG (310 ± 253 mg/dL), e apo CIII (15 ± 4 mg/dL) e valores reduzidos de c-HDL (45 ± 11 mg/dL), sem medicação. Os valores de apoAIV (17,5 ± 10,4 mg/dL) e apoAV (150 ± 135 ng/mL) encontram-se, na maioria dos casos, no intervalo normal assim como os valores de sdLDL (35 ± 18 mg/dL), no entanto alguns casos apresentam valores acima do cut-off para DCV (35 mg/dL). A análise de sdLDL por electroforese foi realizada em 11 doentes, 9 dos quais apresentaram um perfil aterogénico. O valor médio de ApoB destes doentes era de 94 ± 43 mg/dL, mas aproximadamente 70% dos doentes estavam medicados com terapêutica hipolimiante (estatinas e/ou fibratos). Cerca de 30% dos doentes apresentavam DCV prematura. Os resultados obtidos parecem indicar que alterações nos genes estudados influenciam o fenótipo da FCHL. Os níveis séricos de apo CIII encontram-se alterados nesta dislipidemia. Doentes com FCHL, apesar de estarem medicados, apresentam valores elevados de sdLDL, evidenciando o seu elevado risco cardiovascular. A caracterização bioquímica complementa a identificação genética e permite uma melhor avaliação do risco cardiovascular do doente bem como a escolha de uma terapêutica adequada.
- Characterization of pediatric patients from Portuguese FH studyPublication . Abrantes, LB.; Alves, A.C.; Medeiros, A.M.; Correia, S.; Cruz, A.; Lobarinhas, G.; Garcia, P.; Guerra, A.; Mansilha, H.; Martins, E.; Martins, P.; Salgado, J.; Bourbon, M.; on behalf of investigators of Portuguese FH studyThe Portuguese FH Study (PFHS) started in 1999. The aim of the PFHS is to identify the cause of dyslipidemia in patients with a clinical diagnosis of FH. To date, 452 pediatric patients were referred to us, 288 of which are index patients. The aim of this study was to analyse the lipid profile and molecular diagnosis of children recruited for the PFHS.
- Hypercholesterolemia: A disease with expression from childhoodPublication . Espinheira, M.C.; Vasconcelos, C.; Medeiros, A.M.; Alves, A.C.; Bourbon, M.; Guerra, A.Hypercholesterolemia results from an alteration, genetic or acquired, in lipoprotein metabolism. Evidence that hypercholesterolemia is associated with the atherosclerotic process from childhood justifies the screening of high-risk children and initiation of therapy at preschool ages.
- Lysosomal acid lipase deficiency: a hidden disease among cohorts of familial hypercholesterolemia?Publication . Chora, J.R.; Alves, A.C.; Medeiros, A.M.; Mariano, C.; Lobarinhas, G.; Guerra, A.; Mansilha, H.; Cortez-Pinto, H.; Bourbon, M.Highlights: - Dyslipidemia phenotype of patients with familial hypercholesterolemia and lysosomal acid lipase deficiency (LALD) can overlap; - Familial hypercholesterolemia negative patients should be investigated to identify possible LALD patients; - Correct identification of LALD patients is important for patient prognosis. Background: Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder and an unrecognized cause of dyslipidemia. Patients usually present with dyslipidemia and altered liver function and mutations in LIPA gene are the underlying cause of LALD. Objective: The aim of this study was to investigate LALD in individuals with severe dyslipidemia and/or liver steatosis. Methods: Coding, splice regions, and promoter region of LIPA were sequenced by Sanger sequencing in a cohort of mutation-negative familial hypercholesterolemia (FH) patients (n = 492) and in a population sample comprising individuals with several types of dyslipidemia and/or liver steatosis (n = 258). Results: This study led to the identification of LALD in 4 children referred to the Portuguese FH Study, all with a clinical diagnosis of FH. Mild liver dysfunction was present at the age of FH diagnosis; however, a diagnosis of LALD was not considered. No adults at the time of referral have been identified with LALD. Conclusion: LALD is a life-threatening disorder, and early identification is crucial for the implementation of specific treatment to avoid premature mortality. FH cohorts should be investigated to identify possible LALD patients, who will need appropriate treatment. These results highlight the importance of correctly identifying the etiology of the dyslipidemia.
- Pediatric Familial HypercholesterolaemiaPublication . Abrantes, L.B.; Alves, A.C.; Medeiros, A.M.; Correia, S.; Cruz, A.; Ferreira, A.C.; Lobarinhas, G.; Garcia, P.; Guerra, A.; Mansilha, H.; Martins, E.; Martins, P.; Salgado, J.M.; Bourbon, M.; on behalf of investigators of Portuguese FH StudFamilial hypercholesterolemia (FH) is an autosomal dominant disorder associated with high levels of LDL-c and premature CHD (pCHD). Identification of FH in pediatric age is essential for a timely diagnosis and management. This study aims to highlight the importance of FH diagnosis in children.
- Will Familial Hypercholesterolaemia Cohorts Hide Many More Lisosomal Acid Lipase Deficiency Patients?Publication . Chora, J.R.; Alves, A.C.; Medeiros, A.M.; Mariano, C.; Lobarinhas, G.; Guerra, A.; Mansilha, H.; Bourbon, MafaldaAims: Lisosomal Acid Lipase Deficiency (LALD), historical known as Cholesterol Ester Storage Disease (CESD), is an autosomal lisosomal storage recessive disorder and an unrecognized cause of dyslipidaemia. Mutations in LIPA gene are the underlying cause of LALD, being a mutation in the splice site of exon 8 the most common cause of the disease. Patients with LALD present dyslipidaemia and altered liver function. The aim of this work was to analyze LIPA gene in patients with unexplained dyslipidaemia.