4-year Study Shows Newborn Screening Effectively Identifies Infants with Fabry Disease

Newborn screening with enzymatic testing can effectively detect Fabry disease in infants, a four-year study by the public health system in the U.S. state of Missouri suggests.

The study, “Incidence of 4 Lysosomal Storage Disorders From 4 Years of Newborn Screening,” was published in the journal JAMA Pediatrics.

The report describes the efficiency of newborn screening tests in identifying carriers of lysosomal storage disorders, including Fabry, Gaucher, MPS I, and Pompe diseases. Missouri is one of the U.S. states that screens for more rare disorders than those listed in the Recommended Uniform Screening Panel suggested by the U.S. Department of Health and Human Services, a federal agency.

To screen for lysosomal storage disorders, Missouri’s Public Health Laboratory tests for the activity of the enzyme that is defective in a particular disease. For Fabry disease, the test measures the activity of α-galactosidase (GLA), the missing enzyme in Fabry patients.

In what was described by researchers as the longest study to determine the incidence rates of lysosomal disorders in the U.S., screening tests of all infants born in Missouri from 2013 to 2017 were analyzed. Approximately 308,000 newborns were screened.

All four lysosomal storage disorders were screened at the same time for each newborn, using only a single dried blood sample from each child.

Samples testing positive for any disorder were referred for subsequent diagnostic genetic testing and follow-up. A total of 133 infants were identified as having one of the disorders.

Fabry screens tested positive in 179 newborns, of whom 94 were confirmed to have the disease. One had a pseudodeficiency — an altered enzyme but no signs of disease — and six had a genetic alteration of unknown significance or disease onset. A total of 66 infants were false-positives, and 12 samples were either lost to follow-up or further testing was declined.

During the long study period, the incidence rate of Fabry disease in Missouri was 1 in every 3,277 infants born, a frequency comparable to that reported in a similar study in Taiwan.

Newborn screening appears to be a highly reliable test that does not miss positive carriers. To date, none of the infants that tested negative in the screening were later diagnosed with one of the lysosomal storage disorders.

The predictive value of the screening for Fabry disease was 60 percent, meaning that among all those who tested positive in the screen, 60 percent were later confirmed to have the disorder or had a genetic alteration of unknown significance.

Screening helps physicians and families obtain an early diagnosis, which is essential to decide on therapeutic interventions before disease onset and progression.

It also identifies infants with genetic alterations of unknown consequences. These infants need continual follow-up to monitor for potential late-onset disorders, researchers say.

This enzymatic screening method also has technical advantages. It “streamlines the workflow, makes efficient use of limited newborn screening materials, technical staff, and laboratory space, and allows a same-day turn-around time,” the researchers noted.