Preliminary proficiency testing results for succinylacetone in dried blood spots for newborn screening for tyrosinemia type I.
BACKGROUND
Succinylacetone (SUAC) is the primary metabolite accumulated in tyrosinemia type I--an inborn error of metabolism that, if untreated, can cause death from liver failure during the first months of life. Newborn screening laboratories measure SUAC in dried blood spot (DBS) samples to detect asymptomatic tyrosinemia type I. We used panels of SUAC-enriched DBSs to compare and evaluate the performance of these screening tests.


METHODS
We prepared sets of DBS materials enriched with predetermined SUAC concentrations and distributed samples of these materials, along with a screening practices questionnaire, to laboratories that perform SUAC tests. We compared their reported SUAC concentrations and questionnaire responses to identify screening practices that affect SUAC test outcomes.


RESULTS
Data from 2 pilot surveys showed large differences among laboratories in SUAC recoveries, reproducible within-laboratory recoveries, and stable performance of the DBS materials. Results from 257 proficiency test analyses contained a total of 6 false-negative misclassifications. Reported recoveries of added SUAC ranged from 0 to >200%. Low-biased SUAC recoveries were associated with 1 method used by 5 laboratories. All laboratories that reported SUAC recoveries > or =100% used DBS matrix calibrators.


CONCLUSIONS
The wide ranges of SUAC concentrations reported for pilot and proficiency testing specimens demonstrate a need to harmonize quantitative results among laboratories. Although DBS matrix calibrators are important for optimizing SUAC recoveries, the preparation of these calibrators is not standardized among laboratories. Certified DBS-based SUAC calibrators are needed for accuracy and harmonization.
Centers for Disease Control and Prevention, Newborn Screening Quality Assurance Program, Atlanta, GA 30341, USA. bwa1@cdc.gov
Barbara W
BW
Adam
Timothy H
TH
Lim
Elizabeth M
EM
Hall
W Harry
WH
Hannon
D001800:Blood Specimen Collection; D006537:Heptanoates / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D007753:Laboratories; D015997:Neonatal Screening / Q000379:methods*; D010865:Pilot Projects; D011785:Quality Assurance, Health Care; D011795:Surveys and Questionnaires; D020176:Tyrosinemias / Q000097:blood / Q000175:diagnosis*
D006537:Heptanoates; C020804:succinylacetone