Neonatal Screening for Lysosomal Storage Disease

It's technically feasible, but the value is unclear.

Development of enzyme replacement therapies for some lysosomal storage disorders (Gaucher disease, Pompe disease, Fabry disease, and Niemann-Pick disease types A and B) has led to the proposal that newborns be screened for them. To assess the feasibility and appropriateness of including these disorders in newborn screening panels, researchers examined dried blood spots for low acid β-glucocerebrosidase, α-galactosidase, α-glucosidase, and acid sphingomyelinase enzyme activity in 34,736 infants born in Austria in 2010.

First screens identified low enzyme levels in 124 samples; retesting in duplicate samples yielded low enzyme levels in 38 infants. Mutation analysis confirmed lysosomal storage disorders in only 15 of these children, for an overall incidence of 1 in 2315 births. Most mutations (75%) were associated with a mild phenotype with late onset and slow disease progression. Positive predictive values for each test ranged from 32% to 80%.

Comment

These findings show that screening for lysosomal storage disorders is technically feasible, but they raise many ethical questions. The high number of cases is surprising, as is the high number of false positives (in prior research, the incidence of Fabry disease was 1 in 3859 births, the incidence of Pompe disease was 1 in 8684 births, and the incidence of Gaucher disease was 1 in 17,368 births). Authors of an accompanying editorial raise concerns about routine neonatal screening for lysosomal storage disorders but acknowledge that early diagnosis and treatment can be lifesaving for some patients. Pediatricians should be informed about the cost-benefit of neonatal screening tests and participate in their state's decision about whether to include lysosomal storage disorders in neonatal screening panels.

Reviewing Author

F. Bruder Stapleton, MD

Disclosures

Consultant/Advisory BoardCareer Physician

Editorial BoardsUpToDate

Leadership Positions in Professional SocietiesAmerican Society of Pediatric Nephrology Foundation (Chair)

F. Bruder Stapleton, MD

Disclosures

Consultant/Advisory BoardCareer Physician

Editorial BoardsUpToDate

Leadership Positions in Professional SocietiesAmerican Society of Pediatric Nephrology Foundation (Chair)

Citation(s):

Mechtler TP et al. Neonatal screening for lysosomal storage disorders: Feasibility and incidence from a nationwide study in Austria. Lancet 2011 Nov 30; [e-pub ahead of print]. (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61266-X/abstract)

Fletcher J and Wilcken B. Neonatal screening for lysosomal storage disorders. Lancet 2011 Nov 30; [e-pub ahead of print] (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61744-3/fulltext)