Newborn Screening for Lysosomal Storage Disorders
Tue 3:30 PM - Track 3: Newborn Screening
Joseph Orsini
NY State Dept of Health
Joseph Orsini, Monica Martin, Amanda Showers, Michele Caggana.

New York State Department of Health
To determine feasibility and practical limitations of automating a multiplexed tandem mass spectrometry method for screening up to 2,000 newborns/day for the following diseases and their respective enzyme deficiencies: Krabbe (GALC), Gaucher (ABG), Fabry (GLA), and Pompe (GAA) and to determine the range of activities from normal specimens and disease controls.

A multiplex method for screening newborns for the above lysosomal storage disorders was evaluated and modified for high-throughput screening. The modified method was used to measure the enzyme activities of over 7,500 unidentified newborns dried blood spots and diseased controls.

Reductions in reagent volumes were as follows: organic transfer volume by 33%; eluent used for the solid phase extraction by 50% and sample reconstitution volume by 50%. In addition, the quench time was altered. These adjustments reduced processing time, and overall solvent and labware consumption. Tandem MS/MS was complete in 90s and instrumentation andthe preliminary GALC, ABG, GLA, and GAA mean enzyme activities of unidentified newborns (compared with their diseased controls) are 3.74 (0.31), 23.9 (0.43), 13.3 (0.51), and 17.6 (0.42) respectively (all units are ìmol/L/h). These results compared favorably to other data presented in the literature.

These method changes decreased the total processing time of a single plate from 160 to 90 minutes (43% reduction) using our liquid handling equipment, making it feasible for future testing of up to 2000 specimens/day. A schematic of how this could be achieved will be presented along with updates on population data using the revised procedure.

Support for this work was provided by the New York State Department of Health.