Familial hypercholesterolaemia in Portugal

• Published in: Atherosclerosis Vol. 196; no. 2; pp. 633 - 642
• Main Authors: Bourbon, M, Alves, A.C, Medeiros, A.M, Silva, S, Soutar, A.K
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01-02-2008; Elsevier
• Subjects: Adolescent; Adult; Apolipoproteins B - genetics; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Child; Cholesterol; Cholesterol - blood; Chromosome Segregation; Coronary heart disease; Familial hypercholesterolaemia; Female; Haplotypes; Humans; Hyperlipoproteinemia Type II - epidemiology; Hyperlipoproteinemia Type II - genetics; Index patient; Low density lipoprotein receptor; Male; Medical sciences; Middle Aged; Mutation; Mutations; Pedigree; Portugal - epidemiology; Proprotein Convertase 9; Proprotein Convertases; Receptors, LDL - genetics; Serine Endopeptidases - genetics; Mutations; Index patient; Low density lipoprotein receptor; Coronary heart disease; Familial hypercholesterolaemia; Cholesterol; Human; Metabolic diseases; Lipids; Cardiovascular disease; Hyperlipoproteinemia; Lipoprotein; Genetic disease; Vascular disease; Hypercholesterolemia; Atherosclerosis; Mutation; Dyslipemia
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2007.07.019

Abstract Familial hypercholesterolaemia (FH) is characterised clinically by an increased level of circulating LDL cholesterol that leads to lipid accumulation in tendons and arteries, premature atherosclerosis and increased risk of coronary heart disease (CHD). Although Portugal should have about 20,000 cases, this disease is severely under-diagnosed in our country, this being the first presentation of Portuguese data on FH. A total of 602 blood samples were collected from 184 index patients and 418 relatives from several centres throughout Portugal. Fifty-three different mutations were found in 83 index patients, 79 heterozygous and 4 with two defective LDLR alleles. Additionally, 4 putative alterations were found in 8 patients but were not considered mutations causing disease, mainly because they did not co-segregate with hypercholesterolaemia in the families. Three unrelated patients were found to be heterozygous for the APOB3500 mutation and two unrelated patients were found to be heterozygous for a novel mutation in PCSK9 , predicted to cause a single amino acid substitution, D374H. Cascade screening increased the number of FH patients identified genetically to 204. The newly identified FH patients are now receiving counselling and treatment based on the genetic diagnosis. The early identification of FH patients can increase their life expectancy and quality of life by preventing the development of premature CHD if patients receive appropriate pharmacological treatment.