NIH Grants $3.8M to Improve Newborn Screening for 3 Diseases

University at Buffalo researchers are working to boost testing accuracy

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Scientists at the University at Buffalo (UB) in New York have received a five-year $3.8-million grant to develop methods to improve the accuracy of newborn screening for Pompe disease and two other rare genetic disorders.

The project, “Enhancement of Newborn Screening Diagnostic Paradigms to Improve the Efficacy of Treatment for Krabbe Disease, Pompe Disease, and Mucopolysaccharidosis Type 1,” was awarded by the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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Pompe disease is a rare progressive disease caused by mutations in the GAA gene that interfere with the functionality of an enzyme called acid alpha-glucosidase (GAA).

Though there is no cure for Pompe, enzyme replacement therapy can slow the disease’s progression. These medications are most effective when given as early as possible, so an early diagnosis is considered critically important.

“The earlier an intervention can occur, the better will be the child’s quality of life,” Thomas J. Langan, MD, the project’s leader and an associate professor of neurology and pediatrics at UB’s Jacobs School of Medicine and Biomedical Sciences, said in a university press release.

Newborn screening, or NBS, involves testing babies for genetic disorders such as Pompe within the first days of life, usually using a drop of blood collected from the infant via a prick of the heel.

NBS for Pompe disease generally involves measuring the activity of the GAA enzyme, and an infant with low levels can be referred for genetic testing to confirm the diagnosis.

A notable issue with current versions of this type of testing is that they often have high false-positive rates, where children are flagged by the enzymatic test but ultimately end up not having Pompe disease. This can subject parents to unnecessary anxiety and children to needless, and potentially harmful, interventions.

“The screening tests for these diseases are just not sufficiently accurate,” said Langan, who is also a physician with UBMD Neurology and the director of clinical research at UB’s Institute for Myelin and Glia Exploration.

The earlier an intervention can occur, the better will be the child’s quality of life

In previous work on another rare genetic disorder called Krabbe disease, Langan and colleagues showed that using bivariate normal limits (BVNL) for the levels of two disease biomarkers could improve the accuracy of newborn screening for Krabbe, “essentially eliminating the existing false positive problem,” the researchers wrote in the project’s abstract.

“In our preliminary studies on Krabbe disease, our newborn screening test using this approach proved to be between 90 and 92% accurate,” Langan said, noting that current NBS approaches for this condition have accuracies of 10%–20% at best.

“In addition, our approach was able to predict which child would begin to develop Krabbe symptoms before they occur, allowing for the earliest possible interventions,” Langan added.

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In the new project, the researchers will work to expand the use of BVNL in Krabbe NBS, and will also apply this strategy to Pompe disease and another rare genetic disorder called Hurler syndrome (also known as mucopolysaccharidosis type 1).

“Our studies indicate that similar outcomes should be possible with Pompe disease and Hurler syndrome,” Langan said.

The BVNL tool will be applied to NBS for Krabbe and Pompe on all babies born in Buffalo at John R. Oishei Children’s Hospital and at other U.S. sites. Testing for Hurler syndrome will be conducted in babies born at three sites in Japan, where there is a higher incidence of the disease.

If all goes as planned, by the end of the five-year study about 20% of babies born in the U.S. will have undergone this type of screening.

“If the improved prediction of [Krabbe disease], [Hurler syndrome], and [Pompe disease] after NBS is achieved, treatment will be enhanced for these devastating illnesses, and life-threatening treatments for infants will be prevented,” the team wrote in the project’s abstract.