Every expectant parent hopes to welcome a healthy baby into the world. Unfortunately, high-risk newborns with some genetic diseases appear healthy at birth but then rapidly deteriorate—they become lethargic, stop eating, develop seizures, and may progress to coma. For the physicians charged with their care, it’s a race against time to determine which disorder is causing their fragile patient to decline.
These diseases are often caused by malfunctions of the metabolic processes that the body needs to produce essential nutrients and remove harmful toxins. Many of these disorders also have potentially life-saving treatments—but only if they are diagnosed in time.
The challenge stems from the fact that there are hundreds of metabolic diseases, and many have very similar symptoms. Fortunately, for these high-risk newborns and their families, there is hope in the form of new technologies to provide clinicians with the information needed to rapidly diagnose and treat these patients.
Creating New Scientific Tools to Speed Up Diagnosis
Dr. Aimée Dudley’s lab at PNRI has developed a powerful set of scientific tools that addresses a critical, unmet need in the diagnosis of patients with some of these diseases. Although hospitals can now sequence the genomes of critically ill newborns in hours rather than days, it’s often not possible to make a diagnosis based on these data alone. This is because each person’s genome has millions of sequence differences, and while some of these mutations cause disease, many do not. It’s a classic needle in a haystack problem, but one with very high stakes.
A core focus of PNRI is to unravel the powerful mysteries of the human genome to drive future medical breakthroughs—which is exactly what is happening in Dr. Dudley’s lab. Her team developed methods that predict whether a sequence change in a specific human disease gene is likely to cause disease or not. This information can help clinicians diagnose inherited diseases and initiate potentially lifesaving treatments at a faster pace.
One set of inherited metabolic diseases that the Dudley Lab has applied their methods to is known as urea cycle disorders. These disorders are caused by inherited deficiencies in any one of the eight proteins of the urea cycle that prevent toxic levels of ammonia from accumulating in the blood and brain. Without prompt diagnosis and treatment, these metabolic crises can cause irreversible damage or even death.
Partnering With Clinicians to Treat High-Risk Newborns
PNRI values interdisciplinary collaboration and translational applications of our discoveries. Thus, Dr. Dudley works closely with leading pediatricians who specialize in the diagnosis and treatment of infants suffering from urea cycle disorders.
Together, they are working to understand how the Dudley Lab’s results can be used not only to speed diagnosis and inform care, but also to accelerate the development of new treatments and cures for this devastating disease.
The technology built by PNRI’s Dudley Lab puts critical genetic data in the hands of physicians caring for high-risk newborns. Her team’s research offers hope for a brighter future for these families around the globe.