Study Analyzes Incidence Rates of Lysosomal Disorders from 4 Years of Newborn Screening

Study Analyzes Incidence Rates of Lysosomal Disorders from 4 Years of Newborn Screening

A new study reported the incidence rates of Gaucher disease and three other lysosomal storage disorders in the U.S. state of Missouri after four years of newborn screening. The results for Gaucher disease matched those from previous pilot studies, researchers said.

The study, “Incidence of 4 Lysosomal Storage Disorders From 4 Years of Newborn Screening,” appeared in JAMA Pediatrics.

Lysosomal storage disorders are inherited metabolic disorders caused by deficiencies in specific enzymes, resulting in lysosomal functional defects. Lysosomes are small sacs of enzymes that function as the digestive system of a cell, degrading large molecules taken from the outside as well as obsolete components from the cell itself.

Two lysosomal storage disorders, Pompe disease and mucopolysaccharidosis I (MPS I), were recently added to the U.S. Secretary of the Department of Health and Human Services’ Recommended Uniform Screening Panel. Some states such as Missouri have legislative mandates for the universal screening of other lysosomal storage disorders, including Gaucher.

The Missouri State Public Health Laboratory has used a fluorimetric enzyme activity test, a procedure that measures an enzyme’s reaction through changes in the fluorescence of a specific compound, to screen samples from newborns for Gaucher, Pompe, MPS I, and Fabry diseases since January 2013.

This approach “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 scientists wrote.

They analyzed the four-year incidence of these disorders in about 308,000 newborns. The activity of each enzyme implicated in each of the four disorders — acid beta-glucocerebrosidase in the case of Gaucher — was measured simultaneously from dried blood spots. Samples testing positive for a specific lysosomal storage disorder were referred to genetic referral centers for confirmatory tests and follow-up.

Results showed that 133 newborns had a confirmed diagnosis of one of the four disorders, including five who had Gaucher, 32 who had Pompe, 94 who had Fabry, and two who had MPS I. Results from 19 infants were inconclusive, requiring them to be followed-up to monitor for possible late-onset disorders, investigators said.

“These results represent, to our knowledge, the longest prospective, unblinded, full-population testing and follow-up for these [lysosomal storage disorders] in the United States,” researchers wrote.

The incidence rates of Gaucher and MPS I were similar to those reported in prior pilot studies.

Regarding Pompe and Fabry, the scientists noted that Taiwan has the only other newborn screening program with longer clinical follow-up. The incidence of these two diseases in Missouri was similar to that of Taiwan but higher than in the U.S. state of Illinois. In turn, false-positive results were lower in Missouri than in Taiwan. No reports of missed lysosomal storage disorder cases have been seen to date.