Laboratory monitoring of patients with hereditary tyrosinemia type I

Matthew J. Schultz, Brian C. Netzel, Rani H. Singh, Gisele B. Pino, Dimitar K. Gavrilov, Devin Oglesbee, Kimiyo M. Raymond, Piero Rinaldo, Silvia Tortorelli, Wendy E. Smith, Dietrich Matern

Research output: Contribution to journalArticlepeer-review


Background: The prognosis of patients with Hereditary Tyrosinemia Type 1 (HT-1) has greatly improved with early detection through newborn screening and the introduction of nitisinone (NTBC) therapy. A recent guideline calls for periodic monitoring of biochemical markers and NTBC levels to tailor treatment; however, this is currently only achieved through a combination of clinical laboratory tests. We developed a multiplexed assay measuring relevant amino acids, succinylacetone (SUAC), and NTBC in dried blood spots (DBS) to facilitate treatment monitoring. Methods: Tyrosine, phenylalanine, methionine, NTBC and SUAC were eluted from DBS with methanol containing internal standards for each analyte and analyzed by liquid chromatography tandem mass spectrometry over 6.5 min in the multiple reaction monitoring positive mode. Results: Pre-analytical and analytical factors were studied and demonstrated a reliable assay. Chromatography resolved an unknown substance that falsely elevates SUAC concentrations and was present in all samples. To establish control and disease ranges, the method was applied to DBS collected from controls (n = 284) and affected patients before (n = 2) and after initiation of treatment (n = 29). In the treated patients SUAC concentrations were within the normal range over a wide range of NTBC levels. Conclusions: This assay enables combined, accurate measurement of revelevant metabolites and NTBC in order to simplify treatment monitoring of patients with HT-1. In addition, the use of DBS allows for specimen collection at home to facilitate more standardization in relation to drug and dietary treatment.

Original languageEnglish (US)
Pages (from-to)247-254
Number of pages8
JournalMolecular genetics and metabolism
Issue number4
StatePublished - Aug 2020


  • Dried blood spots
  • Hereditary Tyrosinemia type I
  • LC-MS/MS
  • NTBC
  • Nitisinone
  • Succinylacetone

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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