Quantitative determination of succinylacetone in dried blood spots for newborn screening of tyrosinemia type I

  • Magera M
  • Gunawardena N
  • Hahn S
 et al. 
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Background: Tyrosinemia type I (TYR 1) is a severe disorder causing early death if left untreated. While tyrosine can be determined in dried blood spots (DBS), it is not a specific marker for TYR 1 and most often associated with benign transient tyrosinemia of the newborn. Succinylacetone (SUAC) is a specific marker for TYR 1 but not detectable by routine newborn screening. We developed a new assay that determines SUAC in DBS by liquid-chromatography tandem mass spectrometry (LC-MS/MS). Methods: Whole blood is eluted from a 3/16-in. DBS by an aqueous solution containing deuterium labeled SUAC as internal standard (IS). SUAC and IS are oximated, then extracted, butylated, and analyzed by LC-MS/MS. Quantitation is from SUAC spiked calibrator DBS over the range 0-200 muM using selected reaction monitoring of transitions m/z 212 to 156 and m/z 214 to 140 for SUAC and IS, respectively. Analysis time is 5 min. To assess the effectiveness of a two-tier screening approach for TYR 1 we applied this assay to our newborn screening program over the last 15 months. Results: The intra-assay precision was determined for three different levels of SUAC (5, 20, and 50 mumol/L) and the CV calculated to be 4.7, 2.6, and 3.1%, respectively (n = 5). Inter-assay precision CVs were 12.7, 8.2, and 7.8%, respectively on the same samples. SUAC levels in DBS from 10 confirmed TYR 1 cases not treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) were clearly abnormal (16-150 mumol/L; mean: 61 mumol/L; controls:

Author-supplied keywords

  • *newborn screening
  • *succinylacetone/ec [Endogenous Compound]
  • *tyrosinemia/di [Diagnosis]
  • accuracy
  • analytic method
  • aqueous solution
  • article
  • blood analysis
  • blood sampling
  • calibrator
  • chemical reaction
  • clinical article
  • controlled study
  • deuterium
  • extraction
  • human
  • isotope labeling
  • liquid chromatography
  • newborn
  • nitisinone
  • priority journal
  • quantitative analysis
  • reaction analysis
  • standard
  • tandem mass spectrometry
  • tyrosine/ec [Endogenous Compound]

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  • M J Magera

  • N D Gunawardena

  • S H Hahn

  • S Tortorelli

  • G A Mitchell

  • S I Goodman

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