Impaired Cognitive Functioning in Patients with Tyrosinemia Type I Receiving Nitisinone

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.