Tyrosinemia type 1 in Spain: Mutational analysis, treatment and long–term outcome

    loading  Checking for direct PDF access through Ovid


Background:Tyrosinemia type 1 (HT1) is a rare but treatable disease. The aim of the present study was to review the efficacy of long–term treatment of HT1 with nitisinone, expand knowledge about the clinical spectrum of the disease and assess a possible genotype–phenotype correlation.Methods:A retrospective multicenter study was carried out based on questionnaires on genotype, phenotype, therapy and outcome in 34 Spanish patients with HT1.Results:The main manifestations that led to the diagnosis were acute liver failure (55.8%), asymptomatic hepatomegaly (44.1%) and renal tubular dysfunction (29.4%). Laboratory analysis indicated a marked increase of α–fetoprotein and coagulopathy. The most common mutation was IVS6–1(G > T; 66.6% of 24/34 patients for whom mutation analysis was available) and these patients presented less nephrocalcinosis and more hepatomegaly at diagnosis; two novel mutations (c.974C>T, c.398A>T) were found. The mean duration of treatment was 6.73 years. Dietary compliance was very good in 47.1% and good in 20.6%; nitisinone treatment adherence was very good in 85.2% of cases. Mean dose of nitisinone was 0.87 mg/kg per day with average plasma levels of 45.67 μmol/L. Only one patient required liver transplantation after nitisinone and none had hepatocellular carcinoma.Conclusions:Treatment with nitisinone has improved the prognosis of HT1, and compliance is good. In Spain, screening for HT1 by plasma tyrosine and urine succinylacetone determination may be implemented with IVS6–1(G > T) mutational analysis. A correlation between low frequency of nephrocalcinosis and IVS6–1(G > T) mutation was observed.

    loading  Loading Related Articles