Screening Programs May Identify Newborns at Risk for Late-onset Pompe Disease, Other Lysosomal Storage Disorders

Newborn screening for lysosomal storage disorders, including Pompe disease, is much more likely to detect individuals at risk for late-onset disease, according to a four-fear analysis of data from a pilot newborn screening program.

The study “The New York pilot newborn screening program for lysosomal storage diseases: Report of the First 65,000 Infants” was published in the journal Genetics in Medicine.

Early treatment for Pompe disease and other lysosomal storage disorders may improve patients’ long-term outcomes, as these types of diseases may manifest at early infancy.

Lysosomal storage disorders are characterized by shortage of special proteins called enzymes, which reside inside lysosomes and whose function is to break down complex, larger molecules.

That makes screening for lysosomal storage disorders in newborns a likely strategy to reduce disease-related mortality.

However, whether newborns should be screened for lysosomal storage disorders remains a complex debate.

The New York pilot Lysosomal Storage Disorders Newborns Program included 65,605 infants, over 4-years, from six New York hospitals, representing a consenting rate of 73%.

Infants’ dried blood spot samples were used for the screening, after parental consent, for five lysosomal storage disorders — Fabry disease, Gaucher disease, and Niemann-Pick A/B disease (also called Acid Sphingomyelinase Deficiency or ASMD), Pompe disease and later for mucopolysaccharidosis type 1 (MPS 1).

The initial screening was performed using mass spectrometry, a laboratory technique that identifies compounds based on the composition of their molecules and their charges, and known for its effectiveness  and high sensitivity.

In total, the screen detected 69 infants as positive for one of the diseases tested; positives were defined as those whose daily enzymatic activity was below 20 percent. For Pompe disease, the first analysis identified six cases as positives (mean daily acid alpha-glucosidase, GAA activity, the enzyme that underlies the disease, equal or below 15%).

For a more stringent identification, the initial positive hits underwent further testing — enzyme activity, genetic analysis and biomarker quantification— to identify the “true-positives.”

This analysis reduced the cases to 23 (corresponding to 33 percent of the initial pool). For Pompe disease, only one true positive was found.

A true Pompe positive case had, among other features, high levels of glucose tetrasaccharide (Glc4) in the urine, a standard biomarker for Pompe disease.

“Our definition of ‘true positive’ includes all phenotypes [observable characteristics], regardless of severity and predicted age of onset, and is based on genotypic [genetic] and biochemical definitions of disease, rather than a definition based on clinical manifestations,” researchers explained.

All true positives were at risk for late-onset disease confirmed by genetic analysis and low enzyme activity. None of them had developed relevant clinical symptoms at the most recent evaluation.

Overall, “our results suggest that NBS [newborn screening] for LSDs [lysosomal storage disorders] is much more likely to detect individuals at risk for late-onset disease, similar to results from other NBS programs,” the study concluded.

Pompe disease was added to New York’s routine NBS [newborn screening] panel in October 2014.