Nitisinone: new drug. Type 1 tyrosinemia: an effective drug.

(1) Type 1 hereditary tyrosinemia is a rare disease due to an enzyme deficiency. It is associated with life-threatening liver disorders, starting during the very first months of life. If left untreated (other than with a diet low in tyrosine and phenylalanine), most patients die during childhood. Liver transplantation is currently the only treatment to have an effect on survival. (2) Nitisinone is the first drug to be approved in Europe for the treatment of type 1 hereditary tyrosinemia. (3) An international non comparative trial included 207 patients treated with nitisinone in addition to a diet low in tyrosine and phenylalanine. Children treated before the age of 6 months had a far better four-year survival rate than patients treated previously with dietary measures alone (94% versus 60%). The difference was even greater in the subgroups treated before the age of two months (88% versus 29%). When disease onset occurred after the age of 6 months, the ten-year survival rate was about 85% with nitisinone, compared to 60% with dietary measures alone. Only one patient had a neurological crisis during nitisinone therapy. Early nitisinone treatment also reduced the incidence of liver transplantation (13%, compared to 25% with dietary measures alone). (4) Nitisinone seems to have few adverse effects, mainly consisting of thrombocytopenia, leukopenia, cutaneous disorders, and various visual disorders (most of which resolve spontaneously). There may also be a risk of seizures. (5) In practice, nitisinone seems to provide a major benefit for children with type 1 tyrosinemia, provided they are diagnosed and treated during the first 6 months of life. Adverse effects appear to be acceptable but need to be monitored.