Prof Jim Bonham  

Prof Bonham is currently the President of the International Society of Neonatal Screening and national laboratory adviser for newborn screening in the UK on behalf of NHS-England and adviser to the National Screening Committee on behalf of Department of Health and Social Care.

He has a long standing interest in Newborn Screening and the diagnosis of inherited metabolic disorders in childhood and travels extensively, taking part in meetings related to the organisation, conduct and development of Screening in the UK, Europe and further afield.

He has an interest in the potential for the use of genomics in newborn screening alongside biochemical assays.

He also Chairs an International group in partnership with the International Federation of Clinical Chemistry seeking to develop and extend appropriate newborn screening in low and middle income countries.

Galea Lecture: Newborn screening for inherited metabolic disorders: past, present and future

Newborn screening, as we understand it today, began in 1963 when Massachusetts mandated screening for PKU. Conditions were added gradually throughout the 1970s and 1980s often beginning with congenital hypothyroidism and progressing to include congenital adrenal hyperplasia, sickle cell disease and other conditions.

Each addition demanded a new and specific test, but all this changed in the 1990s with a new and disruptive technology, ESI-MS/MS introduced by Millington and Chace.   This enabled the simultaneous detection of a range of inherited metabolic disorders (IMDs) from a single injection.

States in the US and countries in Europe had to determine which they would choose. The problem in making these choices, particularly the phenotypic heterogeneity of screen identified patients, together with the lack of evidence of the impact of screening based on long term outcome studies, made these choices difficult.   To help address this, in 2005 the American College of Medical Genetics described a Recommended Uniform Screening Panel which they believed all states should adopt. This was endorsed by the Secretary’s Advisory Committee in the same year. It currently recommends screening for 35 core and 28 secondary disorders.

In Europe, including the UK, no similar consensus could be achieved, and as a result the range of disorders currently included in national programmes ranges from 2 – 61. There have been a number of attempts to address this variability and most recently the EC funded European Reference Networks for rare disease have formed a Newborn Screening Interest group to consider this issue. Key to any deliberation is the evidence of benefit and an understanding of any resulting harms such as phenotypic uncertainty and the creation of false positive results.

Thirty years after the introduction of MS/MS in newborn screening, a new disruptive technology is being proposed, genomic newborn screening (gNBS) which extends the range of conditions from around 60 to several hundred.   Examples include the Guardian Study in New York, including 450 conditions and the Generation Study in England identifying more than 200 disorders. In the EU, Screen4Care includes a similar number. All of these are research projects and so far, no country is offering gNBS in routine health care for their national programme.

Other than the cost and turnaround time offered by gNBS there are significant ethical and practical issues involved with a DNA based approach in asymptomatic individuals. It is further from the phenotype and, as variants of uncertain significance are generally not reported, the sensitivity of detection is considerably reduced and the penetrance and expression of even highly pathogenic variants may be incomplete.

While the future of biochemical screening seems assured for some decades to come, synergy with easily accessed genomic testing seems likely and may offer new and exciting opportunities to extend and improve newborn screening in the 21st Century.