Recognition, diagnosis and treatment of homozygous familial hypercholesterolemia

References

• Goldstein JL, Hobbs HH, Brown MS, et al. Familial hypercholesterolemia. In: Beaudet AL, Vogelstein B, Kinzler KW, eds. The online metabolic and molecular bases of inherited disease. New York, NY, NY: The McGraw-Hill Companies, Inc.; 2014.
   Google Scholar
• Nordestgaard BGBG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Eur Heart J. 2013;34(45):3478–3490.
   Google Scholar
• Sjouke B, Kusters DM, Kindt I, et al. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype-phenotype relationship, and clinical outcome. Eur Heart J. 2015;36(9):560–565. DOI:10.1093/eurheartj/ehu058.
   Google Scholar
• Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223(2):262–268.
   Google Scholar
• Soutar AK, Naoumova RP. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med. 2007;4(4):214–225.
   Google Scholar
• Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35(32):2146–2157.
   Google Scholar
• Raal FJ, Sjouke B, Hovingh GK, et al. Phenotype diversity among patients with homozygous familial hypercholesterolemia: a cohort study. Atherosclerosis. 2016;248:238–244. DOI:10.1016/j.atherosclerosis.2016.03.009.
   Google Scholar
• Bertolini S, Pisciotta L, Rabacchi C, et al. Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy. Atherosclerosis. 2013;227(2):342–348.
   Google Scholar
• Hegele RA, Ban MR, Cao H, et al. Targeted next-generation sequencing in monogenic dyslipidemias. Curr Opin Lipidol. 2015;26(2):103–113.
   Google Scholar
• Di Taranto MD, D’Agostino MN, Fortunato G. Functional characterization of mutant genes associated with autosomal dominant familial hypercholesterolemia: integration and evolution of genetic diagnosis. Nutr Metab Cardiovasc Dis. 2015;25(11):979–987.
   Google Scholar
• PCSK9 @ www.ucl.ac.uk/ldlr/LOVDv.1.1.0/. http://www.ucl.ac.uk/ldlr/Current/search.php?select_db=PCSK9&srch=all. Accessed 2016 Aug 1
   Google Scholar
• LDLR @ www.ucl.ac.uk/ldlr/LOVDv.1.1.0/. http://www.ucl.ac.uk/ldlr/LOVDv.1.1.0/summary.php?select_db=LDLR&show=sum. Accessed 2016 Aug 1
   Google Scholar
• Usifo E, Leigh SEA, Whittall RA, et al. Low-density lipoprotein receptor gene familial hypercholesterolemia variant database: update and pathological assessment. Ann Hum Genet. 2012;76(5):387–401.
   Google Scholar
• Kusters DM, Huijgen R, Defesche JC, et al. Founder mutations in the Netherlands: geographical distribution of the most prevalent mutations in the low-density lipoprotein receptor and apolipoprotein B genes. Netherlands Hear J. 2011;19(4):175–182.
   Google Scholar
• Leren TP, Finborud TH, Manshaus TE, et al. Diagnosis of familial hypercholesterolemia in general practice using clinical diagnostic criteria or genetic testing as part of cascade genetic screening. Community Genet. 2008;11(1):26–35.
   Google Scholar
• Palacios L, Grandoso L, Cuevas N, et al. Molecular characterization of familial hypercholesterolemia in Spain. Atherosclerosis. 2012;221(1):137–142.
   Google Scholar
• Chiou K-R, Charng M-J. Genetic diagnosis of familial hypercholesterolemia in Han Chinese. J Clin Lipidol. 2016;10(3):490–496.
   Google Scholar
• Austin MA, Hutter CM, Zimmern RL, et al. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am J Epidemiol. 2004;160(5):407–420.
   Google Scholar
• Bertolini S, Cassanelli S, Garuti R, et al. Analysis of LDL receptor gene mutations in Italian patients with homozygous familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1999;19(2):408–418.
   Google Scholar
• Kolansky DM, Cuchel M, Clark BJ, et al. Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia. Am J Cardiol. 2008;102(11):1438–1443.
   Google Scholar
• Thompson GR, Blom DJ, Marais AD, et al. Survival in homozygous familial hypercholesterolaemia is determined by the on-treatment level of serum cholesterol. Eur Heart J. 2017:ehx317. Available from: https://academic.oup.com/eurheartj/article-abstract/doi/10.1093/eurheartj/ehx317/3896244?redirectedFrom=fulltex
   Google Scholar
• Baum SJ, Sijbrands EJG, Mata P, et al. The doctor’s dilemma: challenges in the diagnosis and care of homozygous familial hypercholesterolemia. J Clin Lipidol. 2014;8(6):542–549.
   Google Scholar
• Sjouke B, Defesche JC, Hartgers ML, et al. Double-heterozygous autosomal dominant hypercholesterolemia: clinical characterization of an underreported disease. J Clin Lipidol. 2016;10(6):1462–1469.
   Google Scholar
• Santos RD, Gidding SS, Hegele RA, et al. Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel. Lancet Diabetes Endocrinol. May 2016. 10.1016/S2213-8587(16)30041-9.
   Google Scholar
• Whitfield AJ, Barrett PHR, Van Bockxmeer FM, et al. Lipid disorders and mutations in the APOB gene. Clin Chem. 2004;50(10):1725–1732.
   Google Scholar
• Alves AC, Etxebarria A, Soutar AK, et al. Novel functional APOB mutations outside LDL-binding region causing familial hypercholesterolaemia. Hum Mol Genet. 2014;23(7):1817–1828.
   Google Scholar
• Fernandez-Higuero JA, Etxebarria A, Benito-Vicente A, et al. Structural analysis of APOB variants, p. (Arg3527Gln), p. (Arg1164Thr) and p. (Gln4494del), causing familial hypercholesterolaemia provides novel insights into variant pathogenicity. Sci Rep. 2015;5:18184.
   Google Scholar
• Motazacker MM, Pirruccello J, Huijgen R, et al. Advances in genetics show the need for extending screening strategies for autosomal dominant hypercholesterolaemia. Eur Heart J. 2012;33(11):1360–1366.
   Google Scholar
• Benn M, Watts GF, Tybjærg-Hansen A, et al. Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217. Eur Heart J. 2016;ehw028. DOI:10.1093/eurheartj/ehw028
   Google Scholar
• Kotze MJ, Peeters AV, Langenhoven E, et al. Phenotypic expression and frequency of familial defective apolipoprotein B-100 in Belgian hypercholesterolemics. Atherosclerosis. 1994;111(2):217–225.
   Google Scholar
• Song Q, Cole JW, O’Connell JR, et al. Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the stroke prevention in young women study. Hum Mol Genet. 2006;15(16):2468–2478.
   Google Scholar
• Shen H, Damcott CM, Rampersaud E, et al. Familial defective apolipoprotein B-100 and increased low-density lipoprotein cholesterol and coronary artery calcification in the old order amish. Arch Intern Med. 2010;170(20):1850–1855.
   Google Scholar
• Sabbagh AS, Daher RT, Otrock ZK, et al. ApoB-100 R3500Q mutation in the Lebanese population: prevalence and historical review of the literature. Mol Biol Rep. 2007;34(4):267–270.
   Google Scholar
• Mabuchi H, Nohara A, Noguchi T, et al. Genotypic and phenotypic features in homozygous familial hypercholesterolemia caused by proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutation. Atherosclerosis. 2014;236(1):54–61.
   Google Scholar
• Jiang L, Sun L-Y, Dai Y-F, et al. The distribution and characteristics of LDL receptor mutations in China: a systematic review. Sci Rep. 2015;5:17272.
   Google Scholar
• Raal FJ, Sjouke B, Hovingh GK, et al. Retrospective analysis of cohort database: phenotypic variability in a large dataset of patients confirmed to have homozygous familial hypercholesterolemia. Data Br. 2016;7:1458–1462.
   Google Scholar
• Raal FJ, Hovingh GK, Blom D, et al. Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study. Lancet Diabetes Endocrinol. 2017;5(4):280–290.
   Google Scholar
• Stein EA, Dann EJ, Wiegman A, et al. Efficacy of rosuvastatin in children with homozygous familial hypercholesterolemia and association with underlying genetic mutations. J Am Coll Cardiol. 2017;70(9):1162–1170.
   Google Scholar
• Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385(9965):341–350.
   Google Scholar
• März W, Baumstark MW, Scharnagl H, et al. Accumulation of “small dense” low density lipoproteins (LDL) in a homozygous patient with familial defective apolipoprotein B-100 results from heterogenous interaction of LDL subfractions with the LDL receptor. J Clin Invest. 1993;92(6):2922–2933.
   Google Scholar
• Horinek A, Ceska R, Sobra J, et al. Familial defective apolipoprotein B-100 homozygote with premature coronary atherosclerosis. A case report. J Intern Med. 1999;246(2):235–236.
   Google Scholar
• Gallagher JJ, Myant NB. The affinity of low-density lipoproteins and of very-low-density lipoprotein remnants for the low-density lipoprotein receptor in homozygous familial defective apolipoprotein B-100. Atherosclerosis. 1995;115(2):263–272.
   Google Scholar
• Foody JM, Vishwanath R. Familial hypercholesterolemia/autosomal dominant hypercholesterolemia: molecular defects, the LDL-C continuum, and gradients of phenotypic severity. J Clin Lipidol. 2016 August;10:970–986. DOI:10.1016/j.jacl.2016.04.009
   Google Scholar
• Abifadel M, Varret M, Rabès J-P, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2):154–156.
   Google Scholar
• Cohen JC, Boerwinkle E, Mosley TH, et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354(12):1264–1272.
   Google Scholar
• Fellin R, Arca M, Zuliani G, et al. The history of autosomal recessive hypercholesterolemia (ARH): from clinical observations to gene identification. Gene. 2015;555(1):23–32.
   Google Scholar
• Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest. 2003;111(12):1795–1803.
   Google Scholar
• Arca M, Zuliani G, Wilund K, et al. Autosomal recessive hypercholesterolaemia in Sardinia, Italy, and mutations in ARH: a clinical and molecular genetic analysis. Lancet. 2002;359(9309):841–847.
   Google Scholar
• Pisciotta L, Priore Oliva C, Pes GM, et al. Autosomal recessive hypercholesterolemia (ARH) and homozygous familial hypercholesterolemia (FH): a phenotypic comparison. Atherosclerosis. 2006;188(2):398–405.
   Google Scholar
• Zhou M, Zhao D. Familial hypercholesterolemia in Asian populations. J Atheroscler Thromb. 2016;23(5):539–549.
   Google Scholar
• Wiegman A, Gidding SS, Watts GF, et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36(36):2425–2437.
   Google Scholar
• Raal FJ, Pilcher GJ, Panz VR, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation. 2011;124(20):2202–2207.
   Google Scholar
• Thompson GR, Seed M, Naoumova RP, et al. Improved cardiovascular outcomes following temporal advances in lipid-lowering therapy in a genetically-characterised cohort of familial hypercholesterolaemia homozygotes. Atherosclerosis. 2015;243(1):328–333.
   Google Scholar
• Schmidt HH, Hill S, Makariou EV, et al. Relation of cholesterol-year score to severity of calcific atherosclerosis and tissue deposition in homozygous familial hypercholesterolemia. Am J Cardiol. 1996;77(8):575–580.
   Google Scholar
• Widhalm K, Binder CB, Kreissl A, et al. Sudden death in a 4-year-old boy: a near-complete occlusion of the coronary artery caused by an aggressive low-density lipoprotein receptor mutation (W556R) in homozygous familial hypercholesterolemia. J Pediatr. 2011;158(1):167.
   Google Scholar
• Dumic M, Uroic AS, Francetic I, et al. [Three-year-old boy–a homozygote for familiar hypercholesterolemia]. Lijec Vjesn. 2007;129(5):130–133.
   Google Scholar
• Gautschi M, Pavlovic M, Nuoffer J-M. Fatal myocardial infarction at 4.5 years in a case of homozygous familial hypercholesterolaemia. JIMD Rep. 2012;2:45–50.
   Google Scholar
• Kraft HG, Lingenhel A, Raal FJ, et al. Lipoprotein(a) in homozygous familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2000;20(2):522–528.
   Google Scholar
• Alonso R, Andres E, Mata N, et al. Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation. J Am Coll Cardiol. 2014;63(19):1982–1989.
   Google Scholar
• Seed M, Hoppichler F, Reaveley D, et al. Relation of serum lipoprotein(a) concentration and apolipoprotein(a) phenotype to coronary heart disease in patients with familial hypercholesterolemia. N Engl J Med. 1990;322(0028–4793):1494–1499.
   Google Scholar
• Ooi EMM, Barrett PHR, Watts GF. The extended abnormalities in lipoprotein metabolism in familial hypercholesterolemia: developing a new framework for future therapies. Int J Cardiol. 2013;168(3):1811–1818.
   Google Scholar
• Khera AV, Won -H-H, Peloso GM, et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67(22):2578–2589.
   Google Scholar
• Galaska R, Kulawiak-Galaska D, Wegrzyn A, et al. Assessment of subclinical atherosclerosis using computed tomography calcium scores in patients with familial and nonfamilial hypercholesterolemia. J Atheroscler Thromb. 2015 December. DOI:10.5551/jat.31161.
   Google Scholar
• Rallidis L, Nihoyannopoulos P, Thompson GR. Aortic stenosis in homozygous familial hypercholesterolaemia. Heart. 1996;76(1):84–85.
   Google Scholar
• Awan Z, Alrasadi K, Francis GA, et al. Vascular calcifications in homozygote familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2008;28(4):777–785.
   Google Scholar
• Vongpromek R, Bos S, Ten Kate G-JR, et al. Lipoprotein(a) levels are associated with aortic valve calcification in asymptomatic patients with familial hypercholesterolaemia. J Intern Med. 2014;1–8. DOI:10.1111/joim.12335.
   Google Scholar
• Macchiaiolo M, Buonuomo PS, Valente P, et al. Corneal arcus as first sign of familial hypercholesterolemia. J Pediatr. 2014;164(3):670.
   Google Scholar
• Zech LA, Hoeg JM. Correlating corneal arcus with atherosclerosis in familial hypercholesterolemia. Lipids Health Dis. 2008;7:7.
   Google Scholar
• Yoo E-G. Sitosterolemia: a review and update of pathophysiology, clinical spectrum, diagnosis, and management. Ann Pediatr Endocrinol Metab. 2016;21(1):7–14.
   Google Scholar
• Brautbar A, Leary E, Rasmussen K, et al. Genetics of familial hypercholesterolemia. Curr Atheroscler Rep. 2015;17(4). DOI:10.1007/s11883-015-0491-z
   Google Scholar
• Cuchel M, Meagher EA, Du Toit Theron H, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2013;381(9860):40–46.
   Google Scholar
• Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375(9719):998–1006.
   Google Scholar
• Stefanutti C, Julius U, Watts GF, et al. Toward an international consensus 2014 - integrating lipoprotein apheresis and new lipid-lowering drugs. J Clin Lipidol. 2017;11(4):858.e3-871.e3.
   Google Scholar
• Hudgins LC, Kleinman B, Scheuer A, et al. Long-term safety and efficacy of low-density lipoprotein apheresis in childhood for homozygous familial hypercholesterolemia. Am J Cardiol. 2008;102(9):1199–1204.
   Google Scholar
• Wang A, Richhariya A, Gandra SR, et al. Systematic review of low-density lipoprotein cholesterol apheresis for the treatment of familial hypercholesterolemia. J Am Heart Assoc. 2016;5(7). DOI:10.1161/JAHA.116.003294
   Google Scholar
• Schuff-Werner P, Fenger S, Kohlschein P. Role of lipid apheresis in changing times. Clin Res Cardiol Suppl. 2012;7(Suppl 1):7–14.
   Google Scholar
• Ibrahim M, El-Hamamsy I, Barbir M, et al. Translational lessons from a case of combined heart and liver transplantation for familial hypercholesterolemia 20 years post-operatively. J Cardiovasc Transl Res. 2012;5(3):351–358.
   Google Scholar
• Martinez M, Brodlie S, Griesemer A, et al. Effects of liver transplantation on lipids and cardiovascular disease in children with homozygous familial hypercholesterolemia. Am J Cardiol. 2016;118(4):504–510.
   Google Scholar
• Santos RD, Duell PB, East C, et al. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension. Eur Heart J. 2015;36(9):566–575.
   Google Scholar
• Blom DJ, Averna MR, Meagher EA, et al. Long-term efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in patients with homozygous familial hypercholesterolemia. Circulation. 2017;136(3):332–335.
   Google Scholar
• Underberg J, Cannon C, Larrey D, et al. Abstract 12117: global real-world data on the use of lomitapide in treating homozygous familial hypercholesterolemia: the lomitapide observational worldwide evaluation registry (LOWER), two-year data. Circulation. 2016;134(Suppl 1):A12117 LP–A12117.
   Google Scholar
• Cuchel M, Bloedon LT, Szapary PO, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007;356(2):148–156.
   Google Scholar
• Leipold R, Raal F, Ishak J, et al., The effect of lomitapide on cardiovascular outcome measures in homozygous familial hypercholesterolemia: a modelling analysis. Eur J Prev Cardiol. January 2017: 2047487317730473. 10.1177/2047487317730473
   Google Scholar
• Duell PB, Santos RD, Kirwan B-A, et al. Long-term mipomersen treatment is associated with a reduction in cardiovascular events in patients with familial hypercholesterolemia. J Clin Lipidol. 2016;10(4):1011–1021. DOI:10.1016/j.jacl.2016.04.013.
   Google Scholar
• Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–1722. DOI:10.1056/NEJMoa1615664.
   Google Scholar
• Ray KK, Landmesser U, Leiter LA, et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N Engl J Med. 2017;NEJMoa1615758. DOI:10.1056/NEJMoa1615758.
   Google Scholar
• Stein E, Bays H, Koren M, et al. Efficacy and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients. J Clin Lipidol. 2016;10(5):1212–1222.
   Google Scholar
• Gaudet D, Gipe DA, Pordy R, et al. ANGPTL3 inhibition in homozygous familial hypercholesterolemia. N Engl J Med. 2017;377(3):296–297.
   Google Scholar
• Ajufo E, Cuchel M. Recent developments in gene therapy for homozygous familial hypercholesterolemia. Curr Atheroscler Rep. 2016;18(5):22.
   Google Scholar
• Knowles JW, Rader DJ, Khoury MJ. Cascade screening for familial hypercholesterolemia and the use of genetic testing. JAMA. 2017;318(4):381–382.
   Google Scholar
• Robinson JG, Goldberg AC. Treatment of adults with familial hypercholesterolemia and evidence for treatment: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5(3 Suppl):S18–S29.
   Google Scholar
• Talmud PJ, Shah S, Whittall R, et al. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study. Lancet (London, England). 2013;381(9874):1293–1301.
   Google Scholar
• Wang J, Dron JS, Ban MR, et al. Polygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically Arterioscler Thromb Vasc Biol. 2016;36(12):2439–2445.
   Google Scholar
• Perez-Calahorra S, Sanchez-Hernandez RM, Plana N, et al. Value of the definition of severe familial hypercholesterolemia for stratification of heterozygous patients. Am J Cardiol. 2017;119(5):742–748.
   Google Scholar