Cited by 86Metabolism and Genetic DisordersAmino Acid Enzymes and MetabolismGlycogen Storage Diseases and Myoclonus

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

Al-Dhalimy, M., Overturf, K., Finegold, M., Grompe, M.·2002·Molecular Genetics and Metabolism

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.

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Crossref · 10.1006/mgme.2001.3266

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Authors
Al-Dhalimy, M., Overturf, K., Finegold, M., & Grompe, M.
Affiliations
  • Oregon Health & Science University (US)
  • Texas Children's Hospital (US)
Corresponding author
Grompe, M.
Venue
Molecular Genetics and Metabolism
Publisher
Elsevier BV
Published
2002-01
Volume
75
Issue
1
Pages
38-45
ISSN
1096-7192 (ISSN-L)
OpenAlex
W1971901001
Cited by
86
References
27
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 4 · 2013: 6 · 2012: 3
FWCI
3.28
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular Genetics and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK048252, R01-DK48252)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
Keywords
tyrosinemia type I, NTBC, phenylalanine restriction, hepatocellular carcinoma, succinylacetone, long-term treatment, mouse model, fetal therapy, liver failure, tumor-free survival
MeSH terms
Animals, Cyclohexanones, Diet, Disease Models, Animal, Enzyme Inhibitors, Hydrolases, Nitrobenzoates, Phenylalanine, Tyrosine, Mice, Knockout, Tyrosinemias, Mice

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