There’s a Transformation Happening in Newborn Screening by Whole Genome Sequencing

There is a transformation happening in newborn screening by whole genome sequencing that has the potential to save infants who are currently dying from undiagnosed genetic diseases for which there are treatments.

Between 2015 and 2020 UC San Diego School of Medicine and Rady Children’s Institute for Genomic Medicine conducted an NIH-funded study of how much infant mortality was caused by genetic disease. The numbers surprised me.

Whole-genome sequencing was performed post-mortem on 45 patients who died as infants.

·        31% were found to have a genetic disease that was not diagnosed prior to death.

·        57% of these genetic diseases have an effective treatment.

The Recommended Uniform Screening Panel (RUSP) is a set of 35 federally recommended primary screenings for “actionable disorders”. That means there is a reliable test and a treatment for these conditions. The states are responsible for implementing the screenings but to date, only 21 states screen for all 35 conditions.

If we back up, we find that it takes 5 years on average to have a genetic disorder placed on the RUSP and can take another 10+ years for all states to implement. This incredibly difficult process is out of step with current science. New treatments for genetic disorders are under development at rapid pace.

Rare disease presents challenges for accurate and timely diagnosis – costing rare families time, frustration, financial burden – as well as delay in starting any potential safe and effective therapy. Approximately 80% of rare diseases have identified genetic origins. And better screening can help identify rare diseases among the 4 million infants born in the US annually.

Travere is supporting two transformative new programs in newborn screening (NBS) led by leaders in NBS operating in North Carolina and California that can potentially disrupt NBS as we know it through whole genome sequencing (WGS). NBS using WGS may dramatically shorten the diagnostic journey for families, providing an opportunity for medical intervention that may change the course of a life from birth, before preventable death or disability occur, while also infusing medical research with much needed information about the genetic origins of disease – rare or otherwise – to develop new treatment options.

BeginNGS (pronounced beginnings) is led by Rady Children’s Institute for Genomic Medicine (RCIGM) in San Diego, an NIH Center of Excellence in NBS and WGS. The study includes birthing hospitals throughout the US and abroad. Standard blood spot samples collected at birth for traditional newborn screening are shared to a RCIGM lab for whole-genome sequencing. Analysis is performed with a lens for approximately 400 early onset genetic conditions that have a treatment. Physicians are provided guidance on all available treatments for newborns who test positively.

Led by the nonprofit research institute that spearheaded the groundbreaking work on NBS modernization in 2021, RTI International is launching a major expansion of the Early Check program, a collaboration between RTI, the University of North Carolina at Chapel Hill, also an NIH Center of Excellence in NBS and WGS, and the North Carolina Department of Public Health. This academic-public-private partnership is now poised to offer genome sequencing to parents of newborns in North Carolina and return results for many conditions that are highly actionable in the first two years of life. The Early Check team is developing ways to help new parents learn about the potential that sequencing could offer, to support them in making an informed decision about having their baby’s genome sequenced as part of a research project. They are also developing protocols for providing care to children who are identified on the screening panel. 

One of the challenges of traditional newborn screening today is that there isn’t sufficient follow up to support affected families. For both programs, affected families are provided support and access to specialists.

Another benefit of both programs is the anonymized cutting-edge learnings that come from a growing pool of genetic information paired with clinical experience. So many rare diseases are profoundly difficult to diagnose and treat. By increasing genetic data sets and enabling patients and families to control who has access to the data, researchers can uncover patterns and identify new treatment approaches for rare disorders.

Let’s be clear about what is at risk. If we don’t modernize the newborn screening system, a two-tiered system will grow. Those who can afford it will pay for their own WGS-NBS and we will lose the universal, though currently suboptimal, newborn screening system in the United States.

WGS-NBS through the expanded Early Check and BeginNGS represent a massive leap forward in how the future of newborn screening could save lives and improve health outcomes. We stand by our commitment to rare families to help advance newborn screening and are proud to support both of these groundbreaking initiatives and believe they will help people live with rare disease reach accurate diagnoses faster and lead longer, healthier lives.