Publicação
Insights Into Homozygous Familial Hypercholesterolemia In Portugal
| dc.contributor.author | Medeiros, Ana Margarida | |
| dc.contributor.author | Alves, Ana Catarina | |
| dc.contributor.author | Miranda, Beatriz | |
| dc.contributor.author | Chora, Joana Rita | |
| dc.contributor.author | Aguiar, Patrício | |
| dc.contributor.author | Amaro, Mário | |
| dc.contributor.author | Ferreira, Sofia | |
| dc.contributor.author | Gaspar, Ana | |
| dc.contributor.author | Gonçalves, Filipa Sousa | |
| dc.contributor.author | Lobarinhas, Goreti | |
| dc.contributor.author | Lourenço, Guilherme | |
| dc.contributor.author | Martins, Paula | |
| dc.contributor.author | Antunes, Sofia Moura | |
| dc.contributor.author | Palma, Isabel | |
| dc.contributor.author | Rato, Quitéria | |
| dc.contributor.author | Torres, Diogo | |
| dc.contributor.author | Rico, Miguel Toscano | |
| dc.contributor.author | Travessa, André | |
| dc.contributor.author | Bourbon, Mafalda | |
| dc.date.accessioned | 2026-03-04T16:00:52Z | |
| dc.date.available | 2026-03-04T16:00:52Z | |
| dc.date.issued | 2025-05-04 | |
| dc.description.abstract | Background 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. | eng |
| dc.identifier.uri | http://hdl.handle.net/10400.18/11148 | |
| dc.language.iso | eng | |
| dc.peerreviewed | n/a | |
| dc.rights.uri | N/A | |
| dc.subject | FH | |
| dc.subject | Familial Hyperchosterolemia | |
| dc.subject | Homozygous | |
| dc.subject | Genetic Diagnosis | |
| dc.subject | Portugal | |
| dc.subject | Doenças Cardio e Cérebro-vasculares | |
| dc.title | Insights Into Homozygous Familial Hypercholesterolemia In Portugal | eng |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferenceDate | 2025-05-04 | |
| oaire.citation.conferencePlace | Glasgow, Scotland (UK) | |
| oaire.citation.title | 93rd European Atherosclerosis Society (EAS) Congress, 4-7 may 2025 | |
| oaire.version | http://purl.org/coar/version/c_b1a7d7d4d402bcce |