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NTBC treatment in tyrosinaemia type I: Long-term outcome in French patients

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Summary

We describe a retrospective study of long-term outcome of 46 patients treated and regularly followed in France with 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) for tyrosinaemia type I. Most had initial good response with normalization of liver function and metabolic parameters. Only one infant had no response to treatment and required liver transplantation. Among the 45 long-term treated patients, three underwent secondary liver transplantation: one for cirrhosis and two because of hepatocellular carcinoma. One of the latter died of transplantation complications, so that the overall survival rate was 97.5%. However, 17 of 45 showed persistent abnormal liver imaging (heterogeneous liver) and 6 had cirrhosis. Furthermore, 15 had persistently elevated levels of alpha-fetoprotein, highlighting the question of the persistent risk of carcinoma. Quality of life was usually good but compliance problems were frequent, mainly regarding the low phenylalanine–tyrosine diet. Few adverse effects were observed. A main concern was the high frequency of cognitive impairment causing schooling problems, which may be related to persistent chronic hypertyrosinaemia. In conclusion, this series confirms that NTBC treatment has clearly improved the vital prognosis and quality of life of tyrosinaemia type I patients but that many late complications persist. Long-term studies are necessary to determine whether this drug may prevent or only delay liver complications, andto survey the possible risks of the drug. A more restricted diet could be necessary to prevent the neurological impact of the disease.

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Authors and Affiliations

  1. Pediatric Department, Hôpital d’Enfants, Dijon, France

    A. Masurel-Paulet

  2. Biochemistry Department, Hôpital Bicètre, Le Kremlin-Bicètre, France

    J. Poggi-Bach

  3. Biochemistry Department, Hôpital Debrousse, Lyon, France

    M.-O. Rolland

  4. Hepatology Department, Hôpital Bicètre, Le Kremlin-Bicètre, France

    O. Bernard

  5. Metabolic Unit, Hôpital Edouard Herriot, Lyon, France

    N. Guffon

  6. Metabolic Unit, Hôpital Jeanne de Flandre, Lille, France

    D. Dobbelaere

  7. Gastroenterology Unit, Hôpital de la Timone, Marseille, France

    J. Sarles

  8. Reference Center for Metabolic Diseases, Hôpital Robert Debré, Paris, France

    H. Ogier de Baulny

  9. Metabolic Unit, Hôpital Necker Enfants Malades, Paris, France

    G. Touati

  10. Unité des Maladies Métaboliques, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015, Paris, France

    G. Touati

Authors
  1. A. Masurel-Paulet
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  2. J. Poggi-Bach
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  3. M.-O. Rolland
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  4. O. Bernard
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  5. N. Guffon
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  6. D. Dobbelaere
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  7. J. Sarles
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  8. H. Ogier de Baulny
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  9. G. Touati
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Corresponding author

Correspondence to G. Touati.

Additional information

Communicating editor: Markus Grompe

Competing interests: None declared

References to electronic databases: Tyrosinaemia type I, OMIM 276700. Fumarylacetoacetase, EC 3.7.1.2.

Electronic Supplementary Material

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Supplementary Table S1

Individual data of the 46 long-term treated patients mos = months of age; Tt = NTBC treatment; ANL = Abnormal; Nl = Normal; N = No; Y = Yes (DOC 112 kb)

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Masurel-Paulet, A., Poggi-Bach, J., Rolland, MO. et al. NTBC treatment in tyrosinaemia type I: Long-term outcome in French patients. J Inherit Metab Dis 31, 81–87 (2008). https://doi.org/10.1007/s10545-008-0793-1

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  • DOI: https://doi.org/10.1007/s10545-008-0793-1

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