Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations

Jeffrey M. Chinsky, Rani Singh, Can Ficicioglu, Clara D.M. van Karnebeek, Markus Grompe, Grant Mitchell, Susan E. Waisbren, Muge Gucsavas-Calikoglu, Melissa P. Wasserstein, Katie Coakley, C. Ronald Scott

Research output: Contribution to journalReview articlepeer-review

144 Scopus citations


Tyrosinemia type I (hepatorenal tyrosinemia, HT-1) is an autosomal recessive condition resulting in hepatic failure with comorbidities involving the renal and neurologic systems and long term risks for hepatocellular carcinoma. An effective medical treatment with 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC) exists but requires early identification of affected children for optimal long-term results. Newborn screening (NBS) utilizing blood succinylacetone as the NBS marker is superior to observing tyrosine levels as a way of identifying neonates with HT-1. If identified early and treated appropriately, the majority of affected infants can remain asymptomatic. A clinical management scheme is needed for infants with HT-1 identified by NBS or clinical symptoms. To this end, a group of 11 clinical practitioners, including eight biochemical genetics physicians, two metabolic dietitian nutritionists, and a clinical psychologist, from the United States and Canada, with experience in providing care for patients with HT-1, initiated an evidence- and consensus-based process to establish uniform recommendations for identification and treatment of HT-1. Recommendations were developed from a literature review, practitioner management survey, and nominal group process involving two face-to-face meetings. There was strong consensus in favor of NBS for HT-1, using blood succinylacetone as a marker, followed by diagnostic confirmation and early treatment with NTBC and diet. Consensus recommendations for both immediate and long-term clinical follow-up of positive diagnoses via both newborn screening and clinical symptomatic presentation are provided.

Original languageEnglish (US)
Pages (from-to)1380-1395
Number of pages16
JournalGenetics in Medicine
Issue number12
StatePublished - Dec 2017


  • NTBC
  • hepatocellular carcinoma
  • newborn screening
  • nitisinone
  • tyrosinemia

ASJC Scopus subject areas

  • Genetics(clinical)


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