Performance of succinylacetone assays and their associated proficiency testing outcomes.

BACKGROUND Succinylacetone (SUAC) is the primary metabolic marker for hepatorenal tyrosinemia. MATERIALS AND METHODS We used results reported for dried-blood-spot proficiency testing (PT) specimens and hepatorenal tyrosinemia patients' newborn screening (NBS) samples to demonstrate analytic biases in SUAC recoveries and differences in presumptive clinical classifications. RESULTS SUAC recoveries from non-kit and NeoBase™ kit tandem mass spectrometry methods were markedly different. Kit users that set high cutoff values submitted discordant clinical assessments of "within normal limits" for PT specimens enriched with 10-15 μmol SUAC/L in blood. SUAC levels in tyrosinemia patients' NBS samples analyzed by NeoBase™ kit were lower than those in samples analyzed by non-kit methods. CONCLUSIONS From 2009 to 2011, analytic biases in SUAC recoveries were consistent. Discordant clinical assessments of PT specimens were associated with high cutoff values for NeoBase™ kit results. Method-related differences in SUAC concentrations of tyrosinemia patients' samples were consistent with those of PT specimens.