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Development and Evaluation of Quality Control Dried Blood Spot Materials in Newborn Screening for Lysosomal Storage Disorders

¹ Newborn Screening and Molecular Biology Branch, Centers for Disease Control and Prevention, Atlanta, GA; ² Genzyme, Framingham, MA; ³ Division of Biochemical and Paediatric Genetics, University Children’s Hospital, Vienna, Austria; ⁴ New York Department of Health, Wadsworth Center, Albany, NY, USA

^aAddress correspondence to this author at: Newborn Screening and Molecular Biology Branch, Centers for Disease Control and Prevention, 4770 Buford Highway, Mail Stop F-19, Atlanta, GA 30341. Fax (770) 488-7459; e-mail vdejesus{at}cdc.gov

Background: Lysosomal storage disorders (LSDs) comprise more than 40 genetic diseases that result in the accumulation of products that would normally be degraded by lysosomal enzymes. A tandem mass spectrometry (MS/MS)-based method is available for newborn screening for 5 LSDs, and many laboratories are initiating pilot studies to evaluate the incorporation of this method into their screening panels. We developed and evaluated dried blood spot (DBS) QC materials for LSDs and used the MS/MS method to investigate their suitability for LSD QC monitoring.

Methods: We incubated 3.2-mm punches from DBS controls for 20–24 h with assay cocktails containing substrate and internal standard. Using MS/MS, we quantified the resulting product and internal standard. Samples were run in triplicate for 3 consecutive days, and results were reported as product-to-internal standard ratios and enzyme activity units (µmol/L/h).

Results: Enzyme activity interday imprecision (CV) for the high, medium, and low series were 3.4%–14.3% for galactocerebroside -galactosidase, 6.8%–24.6% for acid -galactosidase A, 7.36%–22.1% for acid sphingomyelinase, 6.2%–26.2% for acid -glucocerebrosidase, and 7.0%–24.8% for lysosomal acid -glucosidase (n = 9). In addition, DBS stored at –20° and 4 °C showed minimal enzyme activity loss over a 187-d period. DBS stored at 37° and 45 °C had lower activity values over the 187-day evaluation time.

Conclusions: Suitable QC materials for newborn screening of LSDs were developed for laboratories performing DBS LSD screening. Good material linearity was observed, with goodness-of-fit values of 0.953 and higher. The QC materials may be used by screening laboratories that perform LSD analysis by MS and/or more conventional fluorescence-based screening methods.

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