Volume 52, Issue 4, April 2023

Universal screening for familial hypercholesterolaemia in newborns: Time for general practice to contribute

Tom Brett   
doi: 10.31128/AJGP-10-22-6581   |    Download article
Cite this article    BIBTEX    REFER    RIS

Familial hypercholesterolaemia (FH), an autosomal dominant genetic condition, affects one in 250 people in Australia. FH is characterised by markedly elevated low-density lipoprotein cholesterol levels from birth, resulting in the accelerated onset of atherosclerotic cardiovascular disease (ASCVD) that would occur in middle years if left untreated.1 The risk of premature ASCVD in FH-positive adults aged 20–39 years is 100-fold greater than individuals without FH who are the same age.2 Effective treatment for FH is available, but 90% of individuals remain undiagnosed and therefore untreated.2 The biggest gaps exist among young people and in primary care.1,3,4 It is time for this situation to be substantially mitigated, and we, as general practitioners (GPs), need to play our part.

The key to the better detection and management of FH is early diagnosis, followed by an appropriate ongoing heart-healthy diet and appropriate medications (usually statins) from 8–10 years of age.3 Children with FH managed this way can expect to live a normal lifespan and avoid premature ASCVD.3,4 The disease begins in childhood, not in adulthood.1,3–5 Thus, widespread FH screening before the disease has time to significantly progress is essential.3

Parents from the Netherlands,6 Australia7 and the UK8 are supportive of phenotypic and genetic testing of children for FH. In the US, various state health departments have implemented universal screening programs through cholesterol testing of children aged 9–11 years.9,10 I am advocating for newborn screening to be considered as an alternative, but promising, option for improved detection of FH in Australia.

Australian newborn bloodspot (NBS) programs have successfully operated for over 50 years and currently screen for 25 rare genetic conditions in the 24–72 hours after birth.11 Newborns screening positive are urgently recalled for confirmatory diagnostic testing, with parents receiving information about the condition and management/treatment options. There is growing international interest in the possible utilisation of genomics to increase the number of conditions screened for in newborns. In Australia, research programs exploring the application of genomics to newborn screening were recently funded by the Medical Research Future Fund.12

A significant advantage of using Australian NBS programs to screen for FH would be their near universal uptake; I therefore believe that adding FH to Australia’s NBS programs should be evaluated using the decision-making criteria of the NBS National Policy Framework.11 This deliberation would determine whether the benefits outweigh the risks, the latter including potential diagnostic stigma, psychological aspects and anxiety about the disorder.13,14 Like other conditions already screened for by NBS programs and fitting the Framework’s criteria, FH is a disease detectable at birth and has a well-known natural history.1,3–5 In addition, it has a safe treatment5 that is both clinically4 and financially15 cost-effective. There are viable tests for FH, and applying these to existing NBS programs appears technically feasible because dried blood spots are suitable sources of both markedly raised total and low-density lipoprotein cholesterol levels,13 as well as suitable for next-generation sequencing analysis.10,16

However, FH differs from other conditions currently included in Australian NBS programs with its mode of inheritance being mostly dominant (a much rarer, more severe recessive form of FH (LDLRAP) also exists).17 Basically, the common form of FH is passed from one generation to the next. Because FH can remain asymptomatic for many decades, multiple blood relatives of babies diagnosed with FH could also unknowingly be affected and have significant risk of ASCVD themselves. Thus, in addition to the benefits to babies identified with FH via the NBS program, reverse cascade testing could deliver familial benefits through subsequent expedited diagnosis of parents, siblings and other blood relatives,18–20 with exclusion from intensive further monitoring of those testing negative. This multiplying beneficial potential from screening newborns for FH would add a new aspect to be deliberated using the NBS National Policy Framework.

Increased GP engagement in cascade testing within families, together with subsequent facilitation of appropriate models of care for those diagnosed with FH, offers enormous untapped opportunities to reduce future ASCVD deaths.3–5 The feasibility and efficacy of child–parent reverse cascade testing for FH in the UK have already been shown.8 In May 2020, Australia introduced a Medicare rebate for specialist genetic testing of high-risk FH phenotypes.21 GPs can subsequently arrange genetic testing among first- and second-degree relatives of patients with a confirmed FH pathogenic variant.

Another difference that would arise if FH were included as part of Australian NBS programs is that considerably more babies would screen positive than currently occurs, because FH is a relatively common condition. The anticipated detection rate of 1 in 250 babies8 would necessitate an appropriate way to ensure that all babies who screen positive are recalled for review and subsequent scaling-up of the delivery of care model for FH to those with a confirmed diagnosis.

My position is that screening for FH should be evaluated for addition to NBS programs11 in Australia. Because almost 90% of Australians visit a GP each year22,23 and up to 100% of newborns are similarly seen, I propose that GPs would be best placed to have a lead role in delivering the FH model of care to diagnosed infants and their families. GPs are ideally placed and experienced in the delivery of care through the lifespan, including the coordination of multidisciplinary care for complex conditions. In the case of FH, this care could include the involvement of paediatricians, cardiologists, lipid specialists, counsellors and genomic medicine, where available.1 New bottom-up infrastructure grounded in primary care is needed that can showcase FH as the exemplar for precision medicine and precision public health, as well as consolidate GPs as stewards and advocates for appropriately applying genetics and genomics. Universal genetic screening of newborns for FH should be provided in Australia.

Competing interests: TB was Chief Investigator on the NHMRC Partnership Grant (GNT1142883) into ‘Improving the detection and management of familial hypercholesterolaemia in Australian general practice’ and has sat on the advisory board and chaired sessions at FH summits supported by Amgen.
Provenance and peer review: Not commissioned, externally peer reviewed.
Funding: None.
Correspondence to:
This event attracts CPD points and can be self recorded

Did you know you can now log your CPD with a click of a button?

Create Quick log
  1. Pang J, Sullivan DR, Brett T, Kostner KM, Hare DL, Watts GF. Familial hypercholesterolaemia in 2020: A leading tier 1 genomic application. Heart Lung Circ 2020;29(4):619–33. doi: 10.1016/j.hlc.2019.12.002. Search PubMed
  2. Wald DS, Bestwick JP, Wald NJ. Child–parent screening for familial hypercholesterolaemia: Screening strategy based on a meta-analysis. BMJ 2007;335(7620):599. doi: 10.1136/bmj.39300.616076.55. Search PubMed
  3. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: Guidance for clinicians to prevent coronary heart disease: Consensus statement of the European Atherosclerosis Society. Eur Heart J 2013;34(45):3478–90a. doi: 10.1093/eurheartj/eht273. Search PubMed
  4. 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):2425–37. doi: 10.1093/eurheartj/ehv157. Search PubMed
  5. Luirink IK, Wiegman A, Kusters DM, et al. 20-Year follow-up of statins in children with familial hypercholesterolemia. N Engl J Med 2019;381(16):1547–56. doi: 10.1056/NEJMoa1816454. Search PubMed
  6. Umans-Eckenhausen MA, Oort FJ, Ferenschild KC, Defesche JC, Kastelein JJ, de Haes JC. Parental attitude towards genetic testing for familial hypercholesterolaemia in children. J Med Genet 2002;39(9):e49. doi: 10.1136/jmg.39.9.e49. Search PubMed
  7. Martin AC, Bell DA, Brett T, Watts GF. Beyond cascade screening: Detection of familial hypercholesterolaemia at childhood immunization and other strategies. Curr Opin Lipidol 2017;28(4):321–27. doi: 10.1097/MOL.0000000000000423. Search PubMed
  8. 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. doi: 10.1056/NEJMoa1602777. Search PubMed
  9. Ritchie SK, Murphy EC, Ice C, et al. Universal versus targeted blood cholesterol screening among youth: The CARDIAC project. Pediatrics 2010;126(2):260–65. doi: 10.1542/peds.2009-2546. Search PubMed
  10. Kanungo S, Patel DR, Neelakantan M, Ryali B. Newborn screening and changing face of inborn errors of metabolism in the United States. Ann Transl Med 2018;6(24):468. doi: 10.21037/atm.2018.11.68. Search PubMed
  11. Australian Government, Department of Health and Aged Care (DHAC). Newborn bloodspot screening – National Policy Framework. Canberra: DHAC, 2018. Available at [Accessed 31 October 2022]. Search PubMed
  12. Australian Government. MDFF-GHF-2022 genomics health futures mission grant opportunity. Canberra, ACT: Australian Government NHMRC, 2022. Available at [Accessed 2 March 2023]. Search PubMed
  13. Held PK, Campbell K, Wiberley-Bradford AE, Lasarev M, Horner V, Peterson A. Analytical validation of familial hypercholesterolemia biomarkers in dried blood spots. Int J Neonatal Screen 2022;8(1):14. doi: 10.3390/ijns8010014. Search PubMed
  14. Henneman L, McBride CM, Cornel MC, Duquette D, Qureshi N. Screening for familial hypercholesterolemia in children: What can we learn from adult screening programs? Healthcare (Basel) 2015;3(4):1018–30. doi: 10.3390/healthcare3041018. Search PubMed
  15. Ademi Z, Norman R, Pang J, et al. Health economic evaluation of screening and treating children with familial hypercholesterolemia early in life: Many happy returns on investment? Atherosclerosis 2020;304:1–8. doi: 10.1016/j.atherosclerosis.2020.05.007. Search PubMed
  16. Hollegaard MV, Grauholm J, Nielsen R, Grove J, Mandrup S, Hougaard DM. Archived neonatal dried blood spot samples can be used for accurate whole genome and exome-targeted next-generation sequencing. Mol Genet Metab 2013;110(1–2):65–72. doi: 10.1016/j.ymgme.2013.06.004. Search PubMed
  17. Vrablik M, Tichý L, Freiberger T, Blaha V, Satny M, Hubacek JA. Genetics of familial hypercholesterolemia: New insights. Front Genet 2020;11:574474. doi: 10.3389/fgene.2020.574474. Search PubMed
  18. Committee on Bioethics; Committee on Genetics; American College of Medical Genetics; Genomics Social; Ethical; Legal Issues Committee. Ethical and policy issues in genetic testing and screening of children. Pediatrics 2013;131(3):620–22. doi: 10.1542/peds.2012-3680. Search PubMed
  19. Wald DS, Bestwick JP. Reaching detection targets in familial hypercholesterolaemia: Comparison of identification strategies. Atherosclerosis 2020;293:57–61. doi: 10.1016/j.atherosclerosis.2019. Search PubMed
  20. Watts GF, Sullivan DR, Hare DL, et al. Integrated guidance for enhancing the care of familial hypercholesterolaemia in Australia. Heart Lung Circ 2021;30(3):324–49. doi: 10.1016/j.hlc.2020.09.943. Search PubMed
  21. Australian Government, Department of Health and Aged Care (DHAC). MBS Online. Medicare Benefits Schedule – Item 73352. Canberra: DHAC, 2020. Available at [Accessed 30 October 2022]. Search PubMed
  22. The Royal Australian College of General Practitioners (RACGP). General practice: Health of the nation 2022. East Melbourne, Vic: RACGP, 2022. Available at [Accessed 2 November 2022]. Search PubMed
  23. Australian Institute of Health and Welfare (AIHW). Medicare-subsidised GP, allied health and specialist health care across local areas: 2013–14 to 2018–19. Canberra: AIHW, 2020. Available at [Accessed 26 October 2022]. Search PubMed

Familial hypercholesterolaemiaNeonatesScreening

Download article