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

Maria Luz Couce, Jaime Dalmau, Mireia Del Toro, Guillem Pintos-Morell, Luís Aldámiz-Echevarría

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34 Citations (Scopus)


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. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.
Original languageEnglish
Pages (from-to)985-989
JournalPediatrics International
Issue number6
Publication statusPublished - 1 Dec 2011


  • acute liver failure
  • genotype-phenotype correlation
  • hereditary tyrosinemia type 1
  • mutations
  • nitisinone


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