a medical professional collecting blood spots from heel of infant

Can Genomic Screening of Newborns Help More Children Born with Rare Diseases?

Newborn screening began in the United States in the 1960s with just one condition: phenylketonuria (PKU). Blood spots are collected from every newborn baby 24 hours after birth and analyzed to detect the preventable disease. With early detection and proper treatment, irreversible brain damage caused by PKU can be prevented.

Today, newborn screening has expanded: In New York state, newborns are screened for about 50 different conditions, most of which are genetic. Early, pre-symptomatic identification allows for early treatment to improve outcomes.

What if we screened for even more rare diseases? It’s a question Wendy Chung, MD, PhD, a pediatrician who is renowned for using genomics to diagnose rare diseases in children, has had in her mind ever since she helped usher in one of the latest additions to the newborn screening list–SMA, which can be treated with gene therapy.

From 2016 to 2017, Chung led the pilot newborn screening study of SMA in New York state that helped lead to nationwide adoption of the test in newborns. “SMA is one of the greatest success stories in terms of being able to diagnose every baby and get them one-and-done gene therapy,” Chung says.

With hundreds of rare diseases now detectable with genetic technology, scanning a newborn’s genome for disease-causing mutations could enable diagnosis before symptoms appear, potentially helping more children, Chung says. Without universal screening, many children are never properly diagnosed and miss the opportunity for the right treatment.

To give every baby a chance at a better life, a new study launched by Chung in New York City called GUARDIAN—Genomic Uniform-screening Against Rare Diseases in All Newborns—is screening 100,000 newborns for 250 medical conditions not currently screened by New York state.

We recently spoke with Chung about the study and what she hopes it will accomplish.

What do you hope widespread genomic screening of newborns will do?

I think expanding the number of diseases we look for could make a radical improvement in the way we diagnose and treat children with rare diseases.

Frankly, I hope it puts me out of business. In my practice, I see many patients with the conditions on our panel. They come to me for a diagnosis, often when they’re 7 or 8 years old, sometimes even in their teens, after years of going from doctor to doctor with symptoms that no one can explain.

Families and pediatricians don’t need to go through those diagnostic odysseys anymore with the genomic technology we now have. We can make the diagnosis at birth.

Diagnosis should be the easiest part of the process. We should focus on what’s really important: the treatment and care of these individuals and their families.

I think genomic screening will also make sure we leave no baby behind. It will provide equitable access to a diagnosis. We want to address health disparities, which we’ve seen happen after screening for SCID (severe combined immunodeficiency disorders) was added to state newborn screening panels. When every newborn is screened, the family’s socioeconomic status is irrelevant.

How do you decide which conditions to include?

We screen for treatable conditions that are symptomatic before the age of 5. We aren’t testing for something that would show up later in life.

Each of these conditions has medications or interventions that prevent or improve the symptoms, although not all conditions can be cured yet. The full list of conditions can be found on our website, Conditions Screened - GUARDIAN Study (guardian-study.org). With early diagnosis and early treatment, we can prevent long-term problems and have better outcomes.

Have any children with rare conditions been identified, resulting in improved care?

It’s still very early and we are still following up on the babies identified through the screening. We have identified one with a genetic cause of hearing loss. In this situation, it’s possible the baby could receive cochlear implants, restoring their hearing and avoiding speech disorders and improving their ability to learn language.

Several babies have been identified with G6PD deficiency. A lack of this enzyme can cause life-threatening anemia when certain medications are taken or after eating certain foods, though most people will not have symptoms if they know what to avoid.

We aim to sequence 100,000 babies, and I estimate that about 1% will receive a diagnosis; parents receive the results about three to six weeks after screening.

At the point a diagnosis is made, parents are connected with treatments, early intervention, the right doctors and nurses and related services, and support systems—whatever is appropriate and necessary.

Can anyone expecting a baby sign up?

For now, GUARDIAN is operating only in New York City at NewYork-Presbyterian hospitals, including Morgan Stanley Children’s Hospital at Columbia University Irving Medical Center.

Parents should also know that there is no cost to enroll in the study. About 75% of parents offered the study have joined and have been happy they enrolled.

More information, including answers to parents’ most frequent questions, is available on our website.


The GUARDIAN study is funded by a combination of private philanthropy and in-kind contributions from Illumina and GeneDx (which provide the technology for screening and the screening services, respectively).