Long-term therapy with NTBC and tyrosine-restricted diet in a murine model of hereditary tyrosinemia type I

M. Al-Dhalimy, K. Overturf, M. Finegold, M. Grompe

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

In human patients with hereditary tyrosinemia type I (HT1) a combination therapy of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3 cyclohexane dione (NTBC) and dietary restriction of phenylalanine and tyrosine is currently widely used. We previously reported that the use of NTBC in a murine model of HT1 abolished acute liver failure but did not prevent the development of hepatocellular carcinoma (HCC) in the setting of nonrestricted protein intake. Here we present the results obtained with higher doses of NTBC plus dietary tyrosine restriction on long-term follow up (>2 years). Liver function tests and succinylacetone levels were completely corrected with this regimen and cancer-free survival was improved when compared to historical controls. However, while no HT1 animals had HCC at age 13 months, the incidence was 2/16 (13%) at age 18 months and 1/6 (17%) after 24 months. Thus, even the most stringent therapy could not prevent the emergence of HCC in the mouse model of HT1, even when initiated prenatally.

Original languageEnglish (US)
Pages (from-to)38-45
Number of pages8
JournalMolecular Genetics and Metabolism
Volume75
Issue number1
DOIs
StatePublished - 2002

Keywords

  • Hepatocarcinoma
  • Hereditary tyrosinemia
  • Liver disease
  • Treatment
  • Tyrosine

ASJC Scopus subject areas

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

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