RARE Daily

GeneDx Reports Progress on Study to End Rare Disease Diagnostic Odyssey

March 21, 2023

Rare Daily Staff

Initial data and analysis from GUARDIAN, a research study recently launched by Columbia University using whole genome sequencing to screen 100,000 newborns for more than 250 genetic conditions not currently included in standard newborn screening, found true positive screening outcomes present in 2.6 percent of the 1,000 newborns enrolled to date.

The findings, reported by GeneDx, which is supporting the whole genome sequencing (WGS) and interpretation services for the GUARDIAN (Genomic Uniform-screening Against Rare Diseases In All Newborns) study, were presented at the ACMG Annual Meeting during the R. Rodney Howell Symposium, Setting the Stage for Genomic Sequencing of All Newborns, on Saturday, March 18, 2023.

As presented by Wendy Chung, a clinical and molecular geneticist at the Kennedy Family Professor of Pediatrics in Medicine and Chief of Clinical Genetics at Columbia University, and principal investigator for the study, of the 1,000 newborns enrolled to date, true positive screening outcomes were present in 2.6 percent of newborns. This included 15 confirmed cases with G6PD deficiency, a genetic disorder not integrated with standard newborn screening. G6PD deficiency is a result of decreased function in an enzyme called G6PD (glucose-6-phosphate dehydrogenase) and causes a breakdown of red blood cells in response to infections, certain drugs, foods, or stress, and is a risk for severe neonatal hyperbilirubinemia.

Additionally, reportable sequence variants from 238 genes screened in the GUARDIAN study were included in a retrospective analysis performed by GeneDx. For almost 25,000 individuals with positive exome or genome sequencing, more than 20 percent of individuals could have identified their genetic disease, on average, 7 to 11 years sooner had they received genome sequencing at birth.

GUARDIAN is sponsored by Columbia University in partnership with New York-Presbyterian, and the New York State Department of Health using whole genome sequencing provided by GeneDx. The goals of the study are to drive earlier diagnosis and treatment to improve the health of the babies who participate, generate evidence to support the expansion of newborn screening through genomic sequencing, and characterize the prevalence and natural history of rare genetic conditions.

“GUARDIAN is quickly teaching us a lot about how to implement genome sequencing in newborns,” said Paul Kruszka, chief medical officer of GeneDx. “We hope studies like the GUARDIAN study are launched across the U.S. to give more families access to this type of informative testing.”

For patients, early diagnosis means doctors and health systems can consider available interventions and therapies more quickly, often leading to improved quality-of-life. Additionally, early diagnosis has financial implications, including saving, on average, $30,000 per case due to reduced hospital stays and unnecessary or ineffective care for patients in the newborn intensive care unit. Further, as more patients are diagnosed with a rare disease, clinical trials can be established that help to more quickly develop therapies that can treat, or perhaps cure, rare diseases.

“The GUARDIAN study has the potential to transform children’s health by equitably diagnosing babies early in life at a time when treatment is most effective,” said Wendy Chung. “Through this study, we are learning how to move genomic medicine forward at scale for the next generation.”

Photo: Wendy Chung, a clinical and molecular geneticist at the Kennedy Family Professor of Pediatrics in Medicine and Chief of Clinical Genetics at Columbia University

Stay Connected

Sign up for updates straight to your inbox.