Impaired cognitive functioning in patients with tyrosinemia type I receiving nitisinone

J Pediatr. 2014 Feb;164(2):398-401. doi: 10.1016/j.jpeds.2013.10.001. Epub 2013 Nov 14.

Abstract

Objective: To examine cognitive functioning in patients with tyrosinemia type I treated with nitisinone and a protein-restricted diet.

Study design: We performed a cross-sectional study to establish cognitive functioning in children with tyrosinemia type I compared with their unaffected siblings. Intelligence was measured using age-appropriate Wechsler Scales. To assess cognitive development over time, we retrieved sequential IQ scores in a single-center subset of patients. We also evaluated whether plasma phenylalanine and tyrosine levels during treatment was correlated with cognitive development.

Results: Average total IQ score in 10 patients with tyrosinemia type I receiving nitisinone was significantly lower compared with their unaffected siblings (71 ± 13 vs 91 ± 13; P = .008). Both verbal and performance IQ subscores differed (77 ± 14 vs 95 ± 11; P < .05 and 70 ± 11 vs 87 ± 15; P < .05, respectively). Repeated IQ measurements in a single-center subset of 5 patients revealed a decline in average IQ score over time, from 96 ± 15 to 69 ± 11 (P < .001). No significant association was found between IQ score and either plasma tyrosine or phenylalanine concentration.

Conclusion: Patients with tyrosinemia type I treated with nitisinone are at risk for impaired cognitive function despite a protein-restricted diet.

Keywords: 2-[2-nitro-4-trifluoromethylbenzoyl]-1, 3-cyclohexanedione; NTBC.

Publication types

  • Multicenter Study

MeSH terms

  • 4-Hydroxyphenylpyruvate Dioxygenase / antagonists & inhibitors
  • Adolescent
  • Child
  • Child Development
  • Child, Preschool
  • Cognition / physiology*
  • Cognitive Dysfunction / epidemiology
  • Cognitive Dysfunction / etiology*
  • Cognitive Dysfunction / physiopathology
  • Cross-Sectional Studies
  • Cyclohexanones / therapeutic use*
  • Disease Progression
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Incidence
  • Male
  • Netherlands / epidemiology
  • Nitrobenzoates / therapeutic use*
  • Prognosis
  • Risk Factors
  • Tyrosinemias / complications*
  • Tyrosinemias / drug therapy
  • Young Adult

Substances

  • Cyclohexanones
  • Enzyme Inhibitors
  • Nitrobenzoates
  • 4-Hydroxyphenylpyruvate Dioxygenase
  • nitisinone