Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

Willem G. van Ginkel, Iris L. Rodenburg, Cary O. Harding, Carla E.M. Hollak, M. Rebecca Heiner-Fokkema, Francjan J. van Spronsen

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations


Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in tyrosine catabolism. TT1 is clinically characterized by acute liver failure, development of hepatocellular carcinoma, renal and neurological problems, and consequently an extremely poor outcome. This review showed that the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) in 1992 has revolutionized the outcome of TT1 patients, especially when started pre-clinically. If started early, NTBC can prevent liver failure, renal problems, and neurological attacks and decrease the risk for hepatocellular carcinoma. NTBC has been shown to be safe and well tolerated, although the long-term effectiveness of treatment with NTBC needs to be awaited. The high tyrosine concentrations caused by treatment with NTBC could result in ophthalmological and skin problems and requires life-long dietary restriction of tyrosine and its precursor phenylalanine, which could be strenuous to adhere to. In addition, neurocognitive problems have been reported since the introduction of NTBC, with hypothesized but as yet unproven pathophysiological mechanisms. Further research should be done to investigate the possible relationship between important clinical outcomes and blood concentrations of biochemical parameters such as phenylalanine, tyrosine, succinylacetone, and NTBC, and to develop clear guidelines for treatment and follow-up with reliable measurements. This all in order to ultimately improve the combined NTBC and dietary treatment and limit possible complications such as hepatocellular carcinoma development, neurocognitive problems, and impaired quality of life.

Original languageEnglish (US)
Pages (from-to)413-426
Number of pages14
JournalPediatric Drugs
Issue number6
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pharmacology (medical)


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