Performance of succinylacetone assays and their associated proficiency testing outcomes

• Published in: Clinical biochemistry Vol. 45; no. 18; pp. 1658 - 1663
• Main Authors: Adam, B.W., Hall, E.M., Meredith, N.K., Lim, T.H., Haynes, C.A., De Jesus, V.R., Hannon, W.H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-12-2012; Elsevier
• Subjects: Analytic bias; Biological and medical sciences; Biological Assay - methods; Biological Assay - standards; Dried Blood Spot Testing; Dried blood spots; Gastroenterology. Liver. Pancreas. Abdomen; Hepatorenal tyrosinemia; Heptanoates - blood; Humans; Infant, Newborn; Investigative techniques, diagnostic techniques (general aspects); Laboratory Proficiency Testing - methods; Laboratory Proficiency Testing - standards; Linear Models; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Neonatal Screening; Newborn screening; Other diseases. Semiology; Proficiency testing; Succinylacetone; Tandem Mass Spectrometry; Tyrosinemia type I; Tandem mass spectrometry; Analytic bias; Hepatorenal tyrosinemia; SUAC; CDC; Tyrosinemia type I; PT; Dried blood spots; NSQAP; MS/MS; QC; DBS; Proficiency testing; Newborn screening; NBS; Neonatal screening; Succinylacetone; Performance evaluation; Neonatal; Prognosis; Bias; Hepatic disease; Hereditary tyrosinemia type 1; Clinical biology; Blood trace; Human; Kidney disease; Urinary system disease; Medical screening; Genetic disease; Newborn; Mass spectrometry MS/MS; Digestive diseases; Performance
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2012.08.007

Succinylacetone (SUAC) is the primary metabolic marker for hepatorenal tyrosinemia.
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.
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 10–15μmol 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.
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.
► We collected results from dried-blood-spot proficiency testing survey specimens. ► We compared reported succinylacetone (SUAC) recoveries and clinical assessments. ► SUAC recoveries from non-kit and Neobase™ kit methods were markedly different. ► From 2009 to 2011, these method-related biases in SUAC recoveries were consistent. ► Discordant clinical assessments were linked to high cutoff values for kit results.