Should Familial Hypercholesterolaemia Be Included in the UK Newborn Whole Genome Sequencing Programme?

Marks D, Thorogood M, Neil HAW, Humphries SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis. 2003;168(1):1–14.

Article  CAS  PubMed  Google Scholar 

Akioyamen LE, Genest J, Shan SD, Reel RL, Albaum JM, Chu A, et al. Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis. BMJ Open. 2017;7(9):e016461.

Article  PubMed  PubMed Central  Google Scholar 

Gratton J, Humphries SE, Futema M. Prevalence of FH-causing variants and impact on LDL-C concentration in European, South Asian, and African ancestry groups of the UK Biobank-Brief report. Arterioscler Thromb Vasc Biol. 2023;43(9):1737–42. The study included 140,439 European, 4067 South Asian and 3906 African participants in the UK BioBank. No statistical difference in the prevalence of an FH-causing variant was observed (1/288 in Europe, 1/260 in Africa and 1/226 in South Asia). Carriers of an FH-causing variant had significantly higher LDL-C concentrations than noncarriers in every ancestry group. There was no difference in mean (statin-use adjusted) LDL-C concentration in FH-variant carriers depending on their ancestry background.

Article  CAS  PubMed  PubMed Central  Google Scholar 

NHS England. NHS long term plan [Internet] 2019 2022 https://www.longtermplan.nhs.uk/wp-content/uploads/2019/01/nhs-long-term-plan.pdf.

Kerr M, Pears R, Miedzybrodzka Z, Haralambos K, Cather M, Watson M, et al. Cost effectiveness of cascade testing for familial hypercholesterolaemia, based on data from familial hypercholesterolaemia services in the UK. Eur Heart J. 2017;38(23):1832–9.

Article  PubMed  PubMed Central  Google Scholar 

Wald DS, Bestwick JP, Wald NJ. Child-parent screening for familial hypercholesterolaemia: screening strategy based on a meta-analysis. BMJ. 2007;335(7620):599.

Article  PubMed  PubMed Central  Google Scholar 

Wald DS, Bestwick JP. Reaching detection targets in familial hypercholesterolaemia: comparison of identification strategies. Atherosclerosis. 2020;293:57–61.

Article  CAS  PubMed  Google Scholar 

Wald DS, Bestwick JP, Morris JK, Whyte K, Jenkins L, Wald NJ. Child-parent familial hypercholesterolemia screening in primary care. N Engl J Med. 2016;375(17):1628–37.

Article  CAS  PubMed  Google Scholar 

National Institute for Health and Care Excellence. Familial hypercholesterolaemia: identification and management National Institute for Health and Care Excellence. NICE clinical guideline (CG71) [internet] 2008 [cited 2022 Nov 24]. https://www.nice.org.uk/guidance/cg71.

Ramaswami U, Humphries SE, Priestley-Barnham L, Green P, Wald DS, Capps N, et al. Current management of children and young people with heterozygous familial hypercholesterolaemia - HEART UK statement of care. Atherosclerosis. 2019;290:1–8.

Article  CAS  PubMed  Google Scholar 

100,000 Genomes Project Pilot Investigators, Smedley D, Smith KR, Martin A, Thomas EA, McDonagh EM, et al. 100,000 Genomes pilot on rare-disease diagnosis in health care - preliminary report. N Engl J Med. 2021;385(20):1868–80. The study involved 4660 participants from 2183 families, who included 161 disorders covering a broad spectrum of rare diseases. Overall, a genetic diagnosis was obtained in 25% of the probands, with diagnostic yields for intellectual disability, hearing disorders and vision disorders ranging from 40 to 55%.

Article  Google Scholar 

Humphries SE, Whittall RA, Hubbart CS, Maplebeck S, Cooper JA, Soutar AK, et al. Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. J Med Genet. 2006;43(12):943–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marduel M, Ouguerram K, Serre V, Bonnefont-Rousselot D, Marques-Pinheiro A, Erik Berge K, et al. Description of a large family with autosomal dominant hypercholesterolemia associated with the APOE p.Leu167del mutation. Hum Mutat. 2013;34(1):83–7.

Article  CAS  PubMed  Google Scholar 

Soutar AK, Naoumova RP. Autosomal recessive hypercholesterolemia. Semin Vasc Med. 2004;4(3):241–8.

Article  PubMed  Google Scholar 

Stitziel NO, Fouchier SW, Sjouke B, Peloso GM, Moscoso AM, Auer PL, et al. Exome sequencing and directed clinical phenotyping diagnose cholesterol ester storage disease presenting as autosomal recessive hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2013;33(12):2909–14.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chora JR, Iacocca MA, Tichý L, Wand H, Kurtz CL, Zimmermann H, et al. The Clinical Genome Resource (ClinGen) familial hypercholesterolemia variant curation expert panel consensus guidelines for LDLR variant classification. Genet Med Off J Am Coll Med Genet. 2022;24(2):293–306.

CAS  Google Scholar 

Haralambos K, Payne J, Datta D, McDowell I, Cramb R, Williams S, Cather M, Neely D, Soran H, Miedzybroadzka Z, Whitmore J. How many patients with a monogenic diagnosis of Familial hypercholesterolemia are currently known in UK lipid clinics? Atherosclerosis Supplements. 2017;28:e8–9.

Article  Google Scholar 

Kwiterovich PO, Levy RI, Fredrickson DS. Neonatal diagnosis of familial type-II hyperlipoproteinaemia. Lancet. 1973;301(7795):118–21.

Article  Google Scholar 

Vuorio AF, Turtola H, Kontula K. Neonatal diagnosis of familial hypercholesterolemia in newborns born to a parent with a molecularly defined heterozygous familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1997;17(11):3332–7.

Article  CAS  PubMed  Google Scholar 

Scientific Steering Committee on behalf of the Simon Broome Register Group. Mortality in treated heterozygous familial hypercholesterolaemia: implications for clinical management. Atherosclerosis. 1999;142:105.

Article  Google Scholar 

Jacobs DR, Woo JG, Sinaiko AR, Daniels SR, Ikonen J, Juonala M, et al. Childhood cardiovascular risk factors and adult cardiovascular events. N Engl J Med. 2022;386(20):1877–88. Among 38,589 participants (3–29 years at recruitment), over a follow-up of ~35 years, there were 319 fatal or non-fatal CVD events. Smoking history as an adolescent, high blood pressure or body mass index were all strongly associated with future CVD risk. The risk of CVD for those with a cholesterol concentration in the top 13% was more than twice as high as for those with a cholesterol level in the bottom 20%.

Article  PubMed  PubMed Central  Google Scholar 

Futema M, Cooper JA, Charakida M, Boustred C, Sattar N, Deanfield J, et al. Screening for familial hypercholesterolaemia in childhood: Avon Longitudinal Study of Parents and Children (ALSPAC). Atherosclerosis. 2017;260:47–55.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Khera AV, Won HH, Peloso GM, Lawson KS, Bartz TM, Deng X, et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67(22):2578–89.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Trinder M, Francis GA, Brunham LR. Association of monogenic vs polygenic hypercholesterolemia with risk of atherosclerotic cardiovascular disease. JAMA Cardiol. 2020;5(4):390–9.

Article  PubMed  PubMed Central  Google Scholar 

France M, Rees A, Datta D, Thompson G, Capps N, Ferns G, et al. HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom. Atherosclerosis. 2016;255:128–39.

Article  CAS  PubMed  Google Scholar 

Cuchel M, Raal FJ, Hegele RA, Al-Rasadi K, Arca M, Averna M, et al. Update on European atherosclerosis society consensus statement on homozygous familial hypercholesterolaemia: new treatments and clinical guidance. Eur Heart J. 2023;44(25):2277–91. New guidelines include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Having LDL-C >0 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. This provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy.

Article  PubMed  PubMed Central  Google Scholar 

Rallidis L, Nihoyannopoulos P, Thompson GR. Aortic stenosis in homozygous familial hypercholesterolaemia. Heart Br Card Soc. 1996;76(1):84–5.

Article  CAS  Google Scholar 

Buja LM, Kovanen PT, Bilheimer DW. Cellular pathology of homozygous familial hypercholesterolemia. Am J Pathol. 1979;97(2):327–57.

CAS  PubMed  PubMed Central  Google Scholar 

Lang TF. Adult presentations of medium-chain acyl-CoA dehydrogenase deficiency (MCADD). J Inherit Metab Dis. 2009;32(6):675–83.

Article  CAS  Google Scholar 

Gidding SS, Wiegman A, Groselj U, Freiberger T, Peretti N, Dharmayat KI, et al. Paediatric familial hypercholesterolaemia screening in Europe: public policy background and recommendations. Eur J Prev Cardiol. 2022;29(18):2301–11. Recommendations are presented aiming to improve the identification of FH and emphasize that every country should have an FH screening programme. These programmes should be adapted from existing strategies to best fit the individual country's healthcare system; governments should provide financial support for these programmes and related care. Further research is recommended to optimize care and implementations.

Article  PubMed  Google Scholar 

Watts GF, Gidding SS, Hegele RA, Raal FJ, Sturm AC, Jones LK, et al. International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia. Nat Rev Cardiol. 2023; A group of international experts systematically developed this guidance for the detection and management of adults or children with heterozygous or homozygous FH, including therapy during pregnancy and the use of apheresis. It updates clinical recommendations and proposes consensus-based implementation strategies with the aim of maximizing the potential benefit for at-risk patients and their families worldwide.

Ramaswami U, Cooper J, Humphries SE, FH Paediatric Register Steering Group. The UK paediatric familial hypercholesterolaemia register: preliminary data. Arch Dis Child. 2017;102(3):255–60.

Article  PubMed  Google Scholar 

Wiegman A, Gidding SS, Watts GF, Chapman MJ, Ginsberg HN, Cuchel M, et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36(36):2425–37.

Article  PubMed  PubMed Central  Google Scholar 

Kinnear FJ, Lithander FE, Searle A, Bayly G, Wei C, Stensel DJ, et al. Reducing cardiovascular disease risk among families with familial hypercholesterolaemia by improving diet and physical activity: a randomised controlled feasibility trial. BMJ Open. 2020;10(12):e044200. This study recruited 22 children and 17 adults with FH who were randomised to either 12-week usual care or intervention aimed to improve dietary, physical activity and sedentary behaviours. The intervention was associated with improvements in several CVD risk factors including LDL-C, with a within-group mean decrease of 8% (children) and 10% (adults).

Article  PubMed  PubMed Central  Google Scholar 

Matthews LA, Rovio SP, Jaakkola JM, Niinikoski H, Lagström H, Jula A, et al. Longitudinal effect of 20-year infancy-onset dietary intervention on food consumption and nutrient intake: the randomized controlled STRIP study. Eur J Clin Nutr. 2019;73(6):937–49.

Article  CAS  PubMed  Google Scholar 

Humphries SE, Cooper J, Dale P, Ramaswami U, FH Paediatric Register Steering Group. The UK Paediatric familial hypercholesterolaemia register: statin-related safety and 1-year growth data. J Clin Lipidol. 2018;12(1):25–32.

Article  PubMed  PubMed Central  Google Scholar 

Ayers JR, Sandler TS, Sandley IN, JR BA, Ayers TS, Sandler IN, Barr A. Risks and interventions for the parentally bereaved child. In: Handbook of children’s coping. Boston, MA: Springer; 1997. p. 215–43.

Google Scholar 

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