Fatiha Bendadi1, Tom J de Koning1, Gepke Visser1, Hubertus C M T Prinsen2, Monique G M de Sain2, Nanda Verhoeven-Duif2, Gerben Sinnema3, Francjan J van Spronsen4, Peter M van Hasselt5. 1. Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. 2. Department of Medical Genetics, Section Metabolic Diagnostics, University Medical Center Utrecht, Utrecht, The Netherlands. 3. Department of Pediatric Psychology, University Medical Center Utrecht, Utrecht, The Netherlands. 4. Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands. 5. Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: p.vanhasselt@umcutrecht.nl.
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.
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.
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