Mayo Clinic Researchers Find New Way to Improve Newborn Screening of Pompe Disease

Researchers at Mayo Clinic have discovered a second-tier test for Pompe disease that has been shown to improve the specificity of newborn screening for the disorder, which would lower the rate of false-positive results.

Pompe disease is a rare inherited disorder caused by the buildup of glycogen (a complex sugar) in the body’s cells. If not diagnosed at birth, children with infantile-onset Pompe disease may suffer from heart problems, breathing issues, muscle impairment, and even death. An enzyme-replacement therapy exists for patients, but the treatment must be initiated before irreversible symptoms develop.

About the Study

Silvia Tortorelli, M.D., Ph.D.

The research of medical geneticist Silvia Tortorelli, M.D., Ph.D., and her Mayo colleagues is outlined in, “Moonlighting Newborn Screening Markers: The Incidental Discovery of a Second-Tier Test for Pompe Disease,” which appeared as an advanced publication in Genetics in Medicine on November 2.

Through the team’s work, a novel biochemical marker was discovered in dried blood spots that not only allows for a faster turnaround time of results but will be more cost-effective than molecular genetic analysis. The new marker was calculated by dividing the creatine/creatinine ratio by the activity of acid A-glucosidase.

According to Dr. Tortorelli, Consultant in the Biochemical Genetics Laboratory, the team used tools created by the Collaborative Laboratory Integrated Reports (CLIR) software to incorporate the new marker into an interpretation algorithm that achieved almost complete segregation between Pompe disease and false-positive cases.

“This new test, once further clinically validated, will allow parents and health care providers to know more quickly and more accurately if a newborn has Pompe disease,” says Dr. Tortorelli. “Treatment can be started right away, offering a better quality of life for these patients.”

Additional validation studies are necessary and undergoing. If confirmed, the biochemical second-tier test will differ from those previously developed because of the potential to become “built in,” where it would be performed in every sample and become part of a newborn’s primary screening (i.e., no additional specimen collections required).

“Our goal is to develop a test that will provide accurate, time-critical results,” says Dr. Tortorelli. “We want to avoid the anxiety and costs associated with false-positive results, which can distress parents, and ultimately do not affect the patients.”

Telling a Bigger Story
The study is actually the first of a pair of papers that were submitted together to tell a bigger story. The second paper, “Precision Newborn Screening for Lysosomal Disorders,” also appeared as an advanced online publication in Genetics in Medicine a week later, on November 9, and summarizes the performance of newborn screening tests sent to Mayo Clinic by the Kentucky Department for Public HealthThis study concluded that CLIR post-analytical interpretive tools can drastically reduce false-positive outcomes, with preliminary evidence of no greater risk of false-negative events, still to be verified by long-term surveillance.

Creating Opportunities
This discovery provides confidence to the possibility of also uncovering more “moonlighting” biochemical markers (a phenomenon by which an enzyme can perform more than one function) for other conditions. As shown through this research, Mayo’s CLIR software is opening the door to the possibility of rapidly screening the whole spectrum of calculated ratios across all types of markers.

Read the team’s paper, “Moonlighting Newborn Screening Markers: The Incidental Discovery of a Second-Tier Test for Pompe Disease,” for further details about the research.

Additional authors on the research team─all from Mayo Clinic, unless noted─are:

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April Josselyn

April Josselyn is a Marketing Associate at Mayo Medical Laboratories. She is the editor of Mayo Clinic PathWays and supports corporate communications strategies and internal communications. She has worked at Mayo Clinic since 2012. Outside of work, April enjoys the outdoors and being "hockey mom" for her two sports-crazed boys.