DPSPDNT - Posters/abstracts em congressos internacionais
URI permanente para esta coleção:
Navegar
Percorrer DPSPDNT - Posters/abstracts em congressos internacionais por autor "Aguiar, Patrício"
A mostrar 1 - 2 de 2
Resultados por página
Opções de ordenação
- Familial and Multifactorial Chylomicronemia Syndrome: Insights from Clinically Diagnosed Cases in PortugalPublication . Alves, Ana Catarina; Ferreira, Maria; Ferreira, Ana Cristina; Padeira, Gonçalo; Gaspar, Ana; Duarte, João Sequeira; Rato, Quitéria; Gonçalves, Filipa Sousa; Aguiar, Patrício; Cruz, Diogo; Bourbon, MafaldaFamilial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive disorder caused by biallelic pathogenic variants in one of five canonical genes, LPL, APOC2, GPIHBP1, APOA5, and LMF1. These variants result in impaired hydrolysis of triglyceride-rich lipoproteins, leading to clinical features such as xanthomas, abdominal pain, hepatomegaly, hepatosplenomegaly, lipemia retinalis, and recurrent pancreatitis. In contrast, Multifactorial Chylomicronemia Syndrome (MCS) often involves monoallelic variants in these genes and/or a high polygenic risk score, contributing to the severe hypertriglyceridemia phenotype. Clinically, FCS and MCS have a similar presentation, requiring genetic analysis for differentiation. This study aimed to clinically and molecularly characterize 42 individuals with severe hypertriglyceridemia in Portugal. Biochemical lipid profile and molecular analysis of the five canonical genes were performed. Moulin's score was applied to 14 cases; for the remaining cases, all data could not be obtained. The average pre-treatment triglyceride level was 2570 mg/dL. Fourteen individuals had pancreatitis, four had hepatomegaly, and three presented with both conditions. Eight cases have biallelic variants: five in LPL (three with identical variants, two with different variants), one in APOC2, one frameshift variant in LMF1 and one total exon 4 deletion in GPIHBP1 (all with identical variants). For these cases, the Moulin score obtained was FCS very likely. Twenty cases have heterozygous variants in LPL, APOA5, LMF1, and GPIHBP1 and were classified as MCS. For one of these cases, the Moulin score was FCS very likely. Ten patients have a negative genetic study, 5 of which had a score of unlikely FCS. Four are still under study. Early identification of FCS is critical to prevent or mitigate its severe complications. A confirmed molecular diagnosis enables accurate differentiation between FCS and MCS, leading to improved clinical management and prognosis. This study underscores the importance of integrating genetic analysis into the diagnostic workup of severe hypertriglyceridemia.
- Insights Into Homozygous Familial Hypercholesterolemia In PortugalPublication . Medeiros, Ana Margarida; Alves, Ana Catarina; Miranda, Beatriz; Chora, Joana Rita; Aguiar, Patrício; Amaro, Mário; Ferreira, Sofia; Gaspar, Ana; Gonçalves, Filipa Sousa; Lobarinhas, Goreti; Lourenço, Guilherme; Martins, Paula; Antunes, Sofia Moura; Palma, Isabel; Rato, Quitéria; Torres, Diogo; Rico, Miguel Toscano; Travessa, André; Bourbon, MafaldaBackground and Aims: Homozygous Familial Hypercholesterolemia (HoFH) is a rare, biallelic semidominant condition caused by pathogenic/likely pathogenic (P/LP) variants in LDLR, APOB, and/or PCSK9 genes. HoFH is characterized by a severe phenotype with LDL-C >400 mg/dL, xanthomas, and early-onset atherosclerotic cardiovascular disease (ASCVD). This work presents the clinical/genetic and follow-up data on individuals genetically identified with HoFH. Methods: A total of 1291 index-cases, with clinical diagnosis of FH, were referred to the Portuguese FH Study. Genetic diagnosis was performed using Sanger sequencing or NGS FH panel. Results: Fifteen individuals were identified as HoFH: 5 with identical biallelic LDLR variants, 8 with different biallelic variants (7 in LDLR, 1 in PCSK9), and 2 with biallelic variants in LDLR and APOB (digenic). Most variants are classified as P/LP; 3 are variants of unknown significance (VUS), but exhibited defects in LDL receptor activity. The cohort included mostly adults (73%) and females (87%), with a median age of 29.9±15.3years at referral (adults: 36.5±12.5years, children/adolescents: 12.0±1.9years). Clinical manifestations included tendon xanthomas (13%) and ASCVD (36%). At referral, all individuals were on statins therapy, with 50% using statin ezetimibe combination, 13% with PCSK9 inhibitors (PCSK9i), and 13% performed LDL apheresis. Five individuals carry at least one null allele (<10% activity), 9 carry defective alleles (10-70% activity), and one has null/null alleles. The latter presented the most severe phenotype (LDL-C=702mg/dL) despite intensive treatment (rosuvastatin, ezetimibe, LDL apheresis, and PCSK9i). Follow-up data were collected for 4 individuals: 2 with defective/defective alleles are now using PCSK9i, while 2 with null/defective and null/null are now using ANGPTL3 inhibitors. Conclusions: In general, Portuguese HoFH individuals are diagnosed late and do not reach the recommended target LDL-C levels. Genetic diagnosis enables precise identification of allele type, allowing more personalized therapeutic approaches, especially for null/null allele carriers who present reduced treatment responsiveness and require therapies independent of LDL receptor function.