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

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Abstract

Purpose of Review

The UK National Health Service (NHS) has recently announced a Newborn Genomes Programme (NGP) to identify infants with treatable inherited disorders using whole genome sequencing (WGS). Here, we address, for familial hypercholesterolaemia (FH), the four principles that must be met for the inclusion of a disorder in the NGP.

Recent Findings

Principle A: There is strong evidence that the genetic variants causing FH can be reliably detected. Principle B: A high proportion of individuals who carry an FH-causing variant are likely to develop early heart disease if left undiagnosed and not offered appropriate treatment. Principle C: Early intervention has been shown to lead to substantially improved outcomes in children with FH. Principle D: The recommended interventions are equitably accessible for all.

Summary

FH meets all the Wilson and Jungner criteria for inclusion in a screening programme, and it also meets all four principles and therefore should be included in the Newborn Genomes Programme.

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Acknowledgments

SEH is an Emeritus BHF Professor and acknowledges funding from the British Heart Foundation (BHF) (RG08/008) and the National Institute for Health Research and University College London Hospitals Biomedical Research Centre. The Paediatric FH Register has been previously supported by funds from the BHF, HEART UK, Cardiac Network Co-ordinating Group Wales, The Royal College of Physicians and a grant from the International Society of Atherosclerosis (Pfizer number 24052829). SEH and UR acknowledge funding from the National Institute for Health and Care Research Health Technology Assessment (NIHR HTA) (Award ID NIHR134993). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Project information available at https://fundingawards.nihr.ac.uk/award/NIHR134993.

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Authors and Affiliations

  1. Centre for Cardiovascular Genetics, Rayne Building, 5 University Street, University College London, London, United Kingdom, WC1E 6JJ

    Steve E Humphries

  2. Lysosomal Disorders Unit, Royal Free London NHS Foundation Trust, Royal Free Hospital, London, United Kingdom, NW3 2QG

    Uma Ramaswami

  3. South Tyneside and Sunderland NHS Foundation Trust, Sunderland Royal Hospital, Sunderland, United Kingdom

    Neil Hopper

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  1. Steve E Humphries
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Correspondence to Uma Ramaswami.

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Competing interests

SEH is the medical director of a UCL Spin-off company (StoreGene) that offers genetic testing for cardiovascular risk including for FH. SEH also reports payment for expert testimony from Verve Therapeutics (to self) and support from the European Atherosclerosis Society to attend EAS 2022 in Milan and 2023 in Mannheim. UR has received advisory board fees from Esperion and has no conflicts of interest related to this manuscript. NH has no conflicts of interest to declare.

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Humphries, S.E., Ramaswami, U. & Hopper, N. Should Familial Hypercholesterolaemia Be Included in the UK Newborn Whole Genome Sequencing Programme?. Curr Atheroscler Rep 25, 1083–1091 (2023). https://doi.org/10.1007/s11883-023-01177-0

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