Genomic Innovation to Support Newborn Screening of Rare Diseases

Written by: Tom Defay, Deputy Head of Diagnostics Strategy & Development

Newborn screening has been one of medicine's greatest success stories, improving the identification of severe genetic disorders before symptoms appear and enabling lifesaving early therapeutic interventions since the late 1960s. However, despite these achievements, newborn screening has lagged behind the genomic revolution driven by scientists mapping the human genome and the rapid advancements in treatment options. Today, while more than 10,000 rare diseases are known, recommended newborn screening panels cover only about 40 core conditions.^1,2 This gap underscores the need for innovative approaches to expand the reach of newborn screening.

An Innovative Approach: BeginNGS^® and Whole Genome Sequencing

To address this gap, the BeginNGS^® (Begin Newborn Genome Sequencing) program pioneers a new approach to newborn screening by seeking to accelerate adoption of whole genome sequencing. Led by Rady Children’s Institute for Genomic Medicine and developed through a consortium including Alexion, AstraZeneca Rare Disease as a founding partner, the goal is to identify infants for thousands of genetic diseases for which therapies exist, before symptoms arise.

Yet, implementing whole genome sequencing as a screening tool introduces new complexities. A major challenge in genomic newborn screening is knowing if a specific genetic change actually leads to disease. Some identified genetic changes have low penetrance, meaning they may only cause disease in a small percentage of people who carry them. This can lead to false alarms, as a newborn could be flagged as being at risk for a disease even though they may never develop symptoms.

In light of this challenge, Alexion and hospital partners are researching ways to improve the accuracy of genomic newborn screening. They are using AI (artificial intelligence) to analyse large, multi-ancestry genetic databases, helping researchers better identify which genetic changes are linked to disease and reduce unnecessary false alarms. This innovative use of AI and diverse data sources is already showing promising results.

A recent study showed that by analysing multi-ancestry databases, genomic newborn screening was much more accurate, reducing false alarms by 97%.³ As the field evolves, continued improvements of processes is essential for making genomic newborn screening clinically viable and ensuring families receive accurate, actionable information.

Expanding Early Intervention Opportunities to Transform Rare Disease Care

The promise of this innovation extends beyond diagnosis—it enables early therapeutic action. As breakthrough treatments become available for rare diseases that were once considered untreatable, being able to identify affected infants before symptoms appear becomes crucial for achieving the best possible outcomes. Through programs like BeginNGS^®, newborn screening can transform the diagnostic journey for families by enabling early action that makes a meaningful difference.