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On average, it takes five to eight years after symptoms appear to get an accurate diagnosis for a rare disease.
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GUARDIAN Study: Genomic Newborn Screening Will Transform the Rare Disease Landscape

The GUARDIAN offers proof of principle that we can implement advanced genomic testing on a large scale

Photo portrait of Paul Kruszka, MD, MPH, FACMG
Paul Kruszka, MD, MPH, FACMG
Photo portrait of Paul Kruszka, MD, MPH, FACMG

Paul Kruszka, MD, MPH, FACMG, is chief medical officer at GeneDx and a clinical geneticist at Children's National Hospital in Washington, DC.

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Published:Jan 23, 2025
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While individually rare, conditions known as rare diseases occur in a collective 1 in 10 Americans. Patients and their families usually find themselves embroiled in a diagnostic odyssey, taking an average of five to eight years after symptoms appear to get an accurate diagnosis. Changing the health system to enable early, pre-symptom diagnosis and treatment would have an enormous impact on millions of families. 

The key to this effort is genetic screening for rare diseases, about 70 percent of which are genetic in origin. As co-author of the large-scale, ongoing GUARDIAN (Genomic Uniform-screening Against Rare Diseases in All Newborns) study with data recently published in the journal JAMA, I’m pleased to report that genomic newborn screening (gNBS) for rare diseases is an accurate, feasible, and actionable way to transform newborn screening to better the lives of children, families, and the health system at large.

Thousands of newborns screened for rare diseases

Data recently published in JAMA from the GUARDIAN study show that gNBS identifies genetic diseases while still asymptomaticenabling doctors to stop disease progression before it begins. Through GUARDIAN, GeneDx has sequenced more than 13,000 newborns for more than 460 clinically actionable early onset genetic conditions. Data from the first 4,000 participants showed that nearly 4 percent had positive screenings, and 92 percent of the true positive findings were in genes not included in traditional newborn screening.

For these asymptomatic infants, the journey to diagnosis may well have been a long one, with potentially damaging consequences of delayed treatment. Some had long QT syndrome, a heart rhythm disorder treatable with medication that can cause sudden cardiac death and often goes undetected until the teenage years. Sequencing also identified several variants that cause epilepsy. GUARDIAN also identified an asymptomatic child with severe combined immune deficiency (SCID) who then underwent a lifesaving bone marrow transplant.

The GUARDIAN study continues to expand toward its enrollment goal of 100,000 participants. Screening is offered free of charge to a diverse population at six New York City hospitals. The acceptance rate has been high—over 70 percent of parents have agreed to screening—parents want this information to provide the best care for their children. 

Actionable results

To do genomic newborn screening ethically and responsibly at scale, gNBS must not only be accurate and feasible but also actionable. All positive findings from the study ensure families can access therapies and treatments that will have an impact on clinical care. In the current environment, we expect the rate of actionable results will grow rapidly. Today, half of FDA applications for investigational new drugs are for rare diseases. New treatments are emerging every month. As technology advances and costs continue to decrease, gNBS will ensure better health outcomes for newborns. 

Scaling gNBS to all newborns

GUARDIAN offers proof of principle that we can implement advanced genomic testing on a large scale. The next step is implementation. Our team at GeneDx is uniquely capable of achieving this, with the scalable genomic technology and massive database of more than 700,000 exomes and genomes to deliver gNBS quickly, equitably, and affordably. The goal is to make gNBS accessible and available for the 3.7 million American children born per year, so that the 1 in 10 with rare diseases can receive actionable diagnoses at birth, avoid the diagnostic odyssey, and have the best chance to prevent disease progression and live healthy lives.