title: Lysosomal storage disorder screening implementation: findings from the first six months of full population pilot testing in Missouri.
abstract: OBJECTIVE
  To evaluate the performance of a statewide full-population pilot study in Missouri on newborn blood spots for screening of lysosomal storage disorders (LSDs) using digital microfluidics.
  
  
  METHODS
  A full-population pilot study using a multiplexed fluorometric enzymatic assay to detect Pompe disease, Fabry disease, Gaucher disease, and mucopolysaccharidosis type I (MPS I) in the Missouri newborn population is ongoing. Provisional cutoff values were determined during a prepilot study. All newborn dried blood spots received at the Missouri State Public Health Laboratory for routine newborn screening were screened for the 4 LSDs during the pilot study. Newborns determined to be screen-positive were referred for confirmatory testing.
  
  
  RESULTS
  The study commenced on January 11, 2013; during the first 6 months, 43,701 specimens were screened, and 27 newborns with a confirmed diagnosis of an LSD genotype (8 with Pompe disease, 1 with Gaucher disease, 15 with Fabry disease, and 3 with MPS I) were identified. These numbers correspond to detection rates of 1:5463 for Pompe disease, 1:43,701 for Gaucher disease, 1:2913 for Fabry disease, and 1:14,567 for MPS I. The positive predictive values were 47% for Pompe disease with 1 lost to follow-up, 10% for Gaucher disease, 58% for Fabry disease with 2 lost to follow-up, and 11% for MPS I with 4 pending.
  
  
  CONCLUSIONS
  The first 6 months of the Missouri LSD pilot study provided the opportunity to validate the effectiveness of the digital microfluidic screening method, refine the cutoffs for detection of these LSDs, and test the entire system of infant referral, follow-up, confirmation, treatment, and screening program communication.
authors.affiliation: Missouri State Public Health Laboratory, Jefferson City, MO.
authors.forename: Patrick V
authors.initials: PV
authors.lastname: Hopkins
authors.affiliation: Missouri State Public Health Laboratory, Jefferson City, MO.
authors.forename: Carlene
authors.initials: C
authors.lastname: Campbell
authors.affiliation: Missouri State Public Health Laboratory, Jefferson City, MO.
authors.forename: Tracy
authors.initials: T
authors.lastname: Klug
authors.affiliation: Missouri State Public Health Laboratory, Jefferson City, MO.
authors.forename: Sharmini
authors.initials: S
authors.lastname: Rogers
authors.affiliation: Missouri State Public Health Laboratory, Jefferson City, MO.
authors.forename: Julie
authors.initials: J
authors.lastname: Raburn-Miller
authors.affiliation: Missouri State Public Health Laboratory, Jefferson City, MO.
authors.forename: Jami
authors.initials: J
authors.lastname: Kiesling
mesh_terms: D000795:Fabry Disease / Q000175:diagnosis; D005260:Female; D005470:Fluorometry; D005776:Gaucher Disease / Q000175:diagnosis; D006009:Glycogen Storage Disease Type II / Q000175:diagnosis; D006801:Humans; D007231:Infant, Newborn; D016464:Lysosomal Storage Diseases / Q000175:diagnosis*; D008297:Male; D044085:Microfluidics / Q000379:methods*; D008923:Missouri; D008059:Mucopolysaccharidosis I / Q000175:diagnosis; D015997:Neonatal Screening / Q000379:methods*; D010865:Pilot Projects; D011237:Predictive Value of Tests