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Tyrosinaemia type I and NTBC (2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐1,3‐cyclohexanedione)
Abstract
In tyrosinaemia type I (McKusick 276700), fatal liver disease results either because of liver failure during infancy or early childhood or because of development of hepatocellular carcinoma during childhood or adolescence. This is caused by toxic metabolites which accumulate because of deficiency of fumarylacetoacetase, the last enzyme in the tyrosine catabolic pathway. NTBC is a potent inhibitor of 4‐hydroxyphenylpyruvate dioxygenase and has been shown to efficiently prevent tyrosine degradation, and production of succinylacetone, in patients with tyrosinaemia. Since the first trial of NTBC treatment for tyrosinaemia type I in 1991, over 220 patients have been treated by the drug using a protocol which includes regular follow‐up with reports of clinical and laboratory investigations to the study centre in Gothenburg, where additional analysis of critical variables is done on regularly collected samples. The course of the disease in patients with acute tyrosinaemia has changed dramatically. Only 10% of the patients have not clinically responded to NTBC treatment. In half of these patients, successful liver transplantation has been performed which has further reduced the mortality rate during infancy to 5%. The international NTBC study has now been going for 5 years and data have emerged that indicate a decreased risk for early development of hepatocellular carcinoma in patients who started treatment at an early age. There are now 101 patients aged 2–8 years who have started NTBC treatment before 2 years of age, and no cancer has developed after 2 years of age among these patients. However, there is no safe age with respect to occurrence of liver cancer, which has been recognized at diagnosis at 1 year of age in one patient and after a few months of treatment in an infant who was given NTBC at 5 months of age.
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“Eye complications do not appear to be common [16,39] but periodic eye examination with a slit lamp may be indicated (for example annually).”
From Recommendations for the management of tyrosinaemia type 1 (2013) · cites this paper as [16]
In the citing paper
“As the plasma concentrations in individuals are variable [16], if rapid assay of plasma nitisinone level is available it may be useful in detecting problems.”
From Recommendations for the management of tyrosinaemia type 1 (2013) · cites this paper as [16]
In the citing paper
“On the standard dose of 1 mg/kg/d, the plasma concentrations in individuals that suppress SA are variable [16,20].”
From Recommendations for the management of tyrosinaemia type 1 (2013) · cites this paper as [16]
In the citing paper
“The risk of long term complications is also reduced [16].”
From Recommendations for the management of tyrosinaemia type 1 (2013) · cites this paper as [16]
Citations
Cites
Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase
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Self-citationOn the enzymic defects in hereditary tyrosinemia.
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“In older patients, the low production may in part be due to self-induced correction of the fumarylacetoacetase defect (Kvittingen et al 1993, 1994), which has been documented to occur in nodules of regenerative liver tissue.”
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Research works printed but not linked: 5
- Dionisi‐Vici C, 1997, Tyrosinemia type I with early metastatic hepatocellular carcinoma: combined treatment with NTBC, chemotherapy and surgical mass removal, J Inher Metab Dis, 20, 15
- Holme E, 1995, Treatment of tyrosinemia type I with an enzyme inhibitor, Int Pediatr, 10, 41
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- Segel I, 1975, Enzyme Kinetics
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Metadata
- Authors
- Holme, E., & Lindstedt, S.
- Affiliations
- Sahlgrenska University Hospital (SE)
- Venue
- Journal of Inherited Metabolic Disease
- Publisher
- Wiley
- Published
- 1998-08
- Volume
- 21
- Issue
- 5
- Pages
- 507-517
- ISSN
- 0141-8955 (ISSN-L)
- 1573-2665
- OpenAlex
- W1567009066
- Cited by
- 264
- References
- 17
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 7 · 2020: 6 · 2019: 10 · 2018: 2 · 2017: 18 · 2016: 7 · 2015: 8 · 2014: 14 · 2013: 11 · 2012: 7
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Inherited Metabolic Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Swedish Cancer Foundation
- Vetenskapsrådet
- 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 › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
- Keywords
- NTBC, tyrosine catabolism, hepatocellular carcinoma prevention, liver transplantation, succinylacetone, early treatment initiation, treatment response
- MeSH terms
- Amino Acid Metabolism, Inborn Errors, Animals, Clinical Trials as Topic, Cyclohexanones, Enzyme Inhibitors, Humans, Nitrobenzoates, Tyrosine, 4-Hydroxyphenylpyruvate Dioxygenase
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