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

Abstract

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.