Characterization of Dried Blood Spot Quality Control Materials for Lysosomal Enzyme Activity Assays Using Digital Microfluidic Fluorometry to Detect Lysosomal Storage Disorders in Newborns.

Newborn bloodspot screening for one or more lysosomal storage disorders (NBS-LSD) is currently performed by many public health NBS laboratories globally. The screening tests measure activities of selected lysosomal enzymes on dried blood spot (DBS) specimens collected from newborns by the heel stick method Because these assays measure enzyme activity, the quantitative results are dependent on the particular analytical method. DBS quality control (DBS QC) materials with assay-specific certified values that span the relevant range from typical to LSD-affected newborns are an important component of quality assurance in NBS laboratories. The Newborn Screening Quality Assurance Program (NSQAP) at the U.S. Centers for Disease Control and Prevention (CDC) provides public health NBS laboratories with DBS QC sets for NBS-LSD comprising four admixtures of pooled umbilical cord blood and a base pool made from leukodepleted peripheral blood and heat-inactivated serum. To evaluate the suitability of these materials for use with digital microfluidics fluorometry (DMF) assays which can currently measure the activity of four enzymes (acid α-galactosidase (GLA); acid β-glucocerebrosidase (GBA); acid α-glucosidase (GAA); and iduronidase (IDUA)), CDC collaborated with the Newborn Screening Unit at the Missouri State Public Health Laboratory (MSPHL). Using MSPHL criteria, we found that the certified results from each of two DBS QC lots collectively spanned the range from typical (screen negative) to enzyme deficient (screen positive) newborn DBS levels for each of the four lysosomal enzymes measured. The range included borderline results that would require repeat screening of the newborn under the MSPHL protocol. We conclude that these DBS QC preparations are suitable for use as external quality control materials for DMF assays used to detect LSDs in newborns.