Tyrosinemia type 1 in Spain: mutational analysis, treatment and long-term outcome.
Pediatr Int
; 53(6): 985-9, 2011 Dec.
Article
en En
| MEDLINE
| ID: mdl-21752152
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tirosina
/
ADN
/
Tirosinemias
/
Ciclohexanonas
/
Mutación
/
Nitrobenzoatos
Tipo de estudio:
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Child
/
Child, preschool
/
Female
/
Humans
/
Male
País/Región como asunto:
Europa
Idioma:
En
Revista:
Pediatr Int
Asunto de la revista:
PEDIATRIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
España