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

Genet Med. 2017 Dec;19(12). doi: 10.1038/gim.2017.101. Epub 2017 Aug 3.


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.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Canada
  • Cyclohexanones / therapeutic use
  • Diet Therapy
  • Disease Management
  • Female
  • Genetic Counseling
  • Genotype
  • Humans
  • Infant, Newborn
  • Liver Transplantation
  • Medication Adherence
  • Neonatal Screening / methods
  • Nitrobenzoates / therapeutic use
  • Phenotype
  • Pregnancy
  • Pregnancy Complications
  • Tyrosinemias / complications
  • Tyrosinemias / diagnosis*
  • Tyrosinemias / etiology
  • Tyrosinemias / therapy*
  • United States


  • Cyclohexanones
  • Nitrobenzoates
  • nitisinone