Novel Genetic Screening Tool Offers Hope for Babies Born With Life-Threatening Metabolic Disorder

New tool will help physicians to rapidly diagnose and treat life-threatening genetic diseases

SEATTLE, WA – May 4, 2023 — Every expectant parent hopes to welcome a healthy baby into the world. Unfortunately, infants with some genetic diseases appear healthy at birth, but then rapidly deteriorate—they become lethargic, stop eating, develop seizures, and may progress to coma—symptoms common to a variety of metabolic disorders. For the physicians charged with their care, it is a race against time to determine which disorder is causing their fragile patient to decline.

For these newborns and their families, there is hope in the form of a new technology that can provide physicians with the information they need to rapidly diagnose and treat these patients. PNRI Senior Investigator Aimée Dudley, Ph.D., and her team have developed a powerful set of scientific tools that allows them to predict whether a change in the genetic sequence of a specific gene is likely to cause disease.

A study published today in the American Journal of Human Genetics describes the tools that the Dudley Lab developed to assess the changes in a genetic sequence (variant) associated with ornithine transcarbamylase deficiency (OTC deficiency), a rare, inherited metabolic disorder. OTC deficiency causes ammonia to accumulate to toxic levels in the blood and brain. Infants born with the severest forms of this disease rapidly develop life-threatening symptoms.

“OTC deficiency is a devastating disease, but we have potentially lifesaving treatments. The key is to make the diagnosis and start treatment in time,” said Andrea Gropman, M.D., Division Chief of Neurodevelopmental Pediatrics and Neurogenetics at Children’s National Hospital, Principle Investigator of the Urea Cycle Rare Disease Consortium (UCDC), and co-author of the study. The UCDC is one of 26 rare disease consortia sponsored by the National Institutes of Health. The UCDC network consists of thirteen U.S. and three international sites.

“This is an excellent example of what can be accomplished by strong partnerships between basic science researchers and clinicians.”
Aimée Dudley, PhD
PNRI Senior Investigator

The tools developed came out of the Dudley Lab’s research using yeast cells–the same type of yeast used in baking–to understand the impact of variants in the genes responsible for human metabolism. By testing the impact of over 1,500 variants in the gene associated with OTC deficiency, they were able to determine which variants were likely to cause severe disease and which were not.

“It is now possible to rapidly sequence the genomes of critically ill newborns. But to use this information, we need to be able to associate the genetic variants we find in a patient with the risk of developing a particular disease,” said Nicholas Ah Mew, M.D., Director of the Inherited Metabolic Disorders Program at Children’s National Hospital, Associate Professor of Pediatrics at The George Washington University, and study co-author. “Having this dataset is a big step toward being able to do that for OTC deficiency.”

The next step will be to evaluate the use of this data in real-life settings. The hope is that clinicians will be able to use this information to identify and treat those newborns at the highest risk of developing severe OTC deficiency more rapidly. “This is an excellent example of what can be accomplished by strong partnerships between basic science researchers and clinicians,” said Dr. Aimée Dudley. “We hope that our data will also accelerate the development of new treatments and cures for OTC deficiency.”

“Now that we have shown that our technology can produce accurate results for OTC deficiency, we are applying it to other rare metabolic diseases. We hope to make this type of data available for many more rare diseases,” said Russell Lo, PNRI Senior Research Project Specialist and lead author of the study.

The technology built by the Dudley Lab at PNRI offers hope for a brighter future for infants with life-threatening metabolic diseases.


About PNRI: Pacific Northwest Research Institute (PNRI) is a nonprofit biomedical research institute, where scientists are using innovative approaches in genetics and genomics to tackle some of the most difficult problems in science and medicine. The institute was founded 67 years ago in Seattle, Washington, as a place where scientists were free to pursue discoveries that promised the highest chance of improving human health. The goal was at the beginning, and remains today, to conduct foundational science leading to impactful medical innovations. To learn more, visit

Media contact: Louise Maxwell
(206) 568-1479