Keywords
Hyperlipoproteinemia Type II
Receptors, LDL
Cholesterol, LDL
How to Cite
Abstract
Familial hypercholesterolemia is a disease caused by mutations in genes related to lipid metabolism, characterized by elevated low-density cholesterol, personal and family history of premature atherosclerotic cardiovascular disease. We present two cases with heterozygous mutation in the promoter of the low-density lipoprotein receptor gene c.-135C>G. The index case had low-density lipoprotein levels above 300 mg/dL at 10 years old, suffered a major cardiovascular event at the age of 40, and a stroke at 48. At the age of 52, a clinical geneticist built a genogram that suggested an autosomal dominant inheritance pattern of familial hypercholesterolemia and performed a molecular panel for the patient and her daughter at 26 years old. Both cases presented therapeutic failure with lovastatin monotherapy. A significant reduction in cholesterol levels was achieved with dual therapy, in the case 1 with alirocumab+rosuvastatin and case 2 with atorvastatin+ezetimibe.
References
Humphries SE, Cooper JA, Seed M, Capps N, Durrington PN, Jones B, et al. Coronary heart disease mortality in treated familial hypercholesterolaemia: Update of the UK Simon Broome FH register. Atherosclerosis. 2018;274:41-46.
Defesche JC, Gidding SS, Harada-Shiba M, Hegele RA, Santos RD, Wierzbicki AS. Familial hypercholesterolaemia. Nat Rev Dis Primers. 2017;3:17093.
Vallejo-Vaz AJ, Ray KK. Epidemiology of familial hypercholesterolaemia: Community and clinical. Atherosclerosis. 2018;277:289-297.
Perez de Isla L, Alonso R, Watts GF, Mata N, Saltijeral-Cerezo A, Muñiz O, et al. Attainment of LDL-Cholesterol Treatment Goals in Patients With Familial Hypercholesterolemia: 5-Year SAFEHEART Registry Follow-Up. J Am Coll Cardiol. 2016;67(11):1278-1285.
Santos RD, Bourbon M, Alonso R, Cuevas A, Vasques-Cardenas NA, Pereira AC, et al. Clinical and molecular aspects of familial hypercholesterolemia in Ibero-American countries. J Clin Lipidol. 2017;11(1):160-166.
Rincón EA, Mesa JEG, Pachajoa HM. Caracterización clínica y molecular en hipercolesterolemia familiar homocigota. Rev la Fac Med. 2018;66:505–508.
Ruiz ÁJ, Patiño LF, Amaya K, Gómez JE, Ordónez F, Paternina S. Hipercolesterolemia familiar: serie de 36 casos con fenotipo de hipercolesterolemia familiar homocigótica. Rev Colomb Cardiol. 2020;27:498–507.
López G, Bernal LM, Gelvez N, Gómez LF, Nova A, Sánchez AI, et al. Mutational analysis of the LDLR gene in a cohort of Colombian families with familial hypercholesterolemia. Atherosclerosis. 2018;277:434-439.
Abifadel M, Boileau C. Genetic and molecular architecture of familial hypercholesterolemia. J Intern Med. 2023;293(2):144-165.
World Health Organization. Familial hypercholesterolaemia (FH): report of a second WHO consultation [Internet]. Geneva: World health organization Human Genetics Programme; 1998. [cited 2021 May 25]. Available from: https:// apps.who.int/iris/handle/10665/66346.
Williams RR, Hunt SC, Schumacher MC, Hegele RA, Leppert MF, Ludwig EH, et al. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol. 1993;72(2):171- 176.
Medeiros AM, Bourbon M. Genetic Testing in Familial Hypercholesterolemia: Is It for Everyone?. Curr Atheroscler Rep. 2023;25(4):127- 132.
National Institute for Health and Care Excellence. Familial hypercholesterolaemia: identification and management. Londres. NICE; 2008. https://www. nice.org.uk/guidance/cg71
Raal FJ, Hovingh GK, Catapano AL. Familial hypercholesterolemia treatments: Guidelines and new therapies. Atherosclerosis. 2018;277:483–492.
Suryawanshi YN, Warbhe RA. Familial Hypercholesterolemia: A Literature Review of the Pathophysiology and Current and Novel Treatments. Cureus. 2023;15(11):e49121.
Pérez de Isla L, Díaz-Díaz JL, Romero MJ, Muñiz-Grijalvo O, Mediavilla JD, Argüeso R, et al. Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study. Circulation. 2023;147(19):1436-1443.
Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015;372(25):2387-2397.
Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008;358(14):1431-1443.
Raal F, Scott R, Somaratne R, Bridges I, Li G, Wasserman SM, et al. Low-density 79 Septiembre-diciembre Familial hypercholesterolemia due to an heterozygous LDLR promoter mutation: a case report lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation. 2012;126(20):2408- 2417.
Rader DJ, Kastelein JJ. Lomitapide and mipomersen: two first-in-class drugs for reducing low-density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia. Circulation. 2014;129(9):1022-1032.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2024 Médicas UIS