Use of Molecular Genetic Analyses in Danish Routine Newborn Screening

Abstract

Historically, the analyses used for newborn screening (NBS) were biochemical, but increasingly, molecular genetic analyses are being introduced in the workflow. We describe the application of molecular genetic analyses in the Danish NBS programme and show that second-tier molecular genetic testing is useful to reduce the false positive rate while simultaneously providing information about the precise molecular genetic variant and thus informing therapeutic strategy and easing providing information to parents. When molecular genetic analyses are applied as second-tier testing, valuable functional data from biochemical methods are available and in our view, such targeted NGS technology should be implemented when possible in the NBS workflow. First-tier NGS technology may be a promising future possibility for disorders without a reliable biomarker and as a general approach to increase the adaptability of NBS for a broader range of genetic diseases, which is important in the current landscape of quickly evolving new therapeutic possibilities. However, studies on feasibility, sensitivity, and specificity are needed as well as more insight into what views the general population has towards using genetic analyses in NBS. This may be sensitive to some and could have potentially negative consequences for the NBS programme.

Current State and Innovations in Newborn Screening: Continuing to Do Good and Avoid Harm

“…Many countries have already adopted the use of genetic, second-tier DNA tests as a part of their NBS programmes [ 40 , 41 ], and for some conditions, this has shown a great benefit by excluding healthy carriers or pseudo-deficient individuals.…”

Genomic-Based Newborn Screening for Inborn Errors of Immunity: Practical and Ethical Considerations

“…Secondly, the result can lead parents to request treatment and for physicians to provide it even though it is not warranted. In the words of Lund et al, there is a risk of ‘reporting of benign variants or variants for late-onset diseases, leading to unnecessary medicalising of the child, giving unnecessary treatment and creating patients-in-waiting’ [ 33 ]. Overtreatment can be harmful to the individual and is costly to society.…”

Expanded newborn bloodspot screening: developed country examples and what can be done in Turkey

“…The number of diseases/disorders screened by the 12 countries is highly variable and ranges from 5-51. The number of diseases/conditions screened are as follows: 32 in Australia (18), 25 in Ontario, Canada (19), 19 in Germany (20)(21)(22) 19 in Denmark (22,23), 9 in the UK (24), 12 in Israel (25), 40 in Italy (26), 25 in the Netherlands (27), 26 in New Zealand (28), 26 in Norway (29), 5 in Turkey (30) and 51 in the New York, USA (31).…”