Neurocognitive outcome in patients with hypertyrosinemia type I after long‐term treatment with NTBC

Abstract

Objective: The implementation of NTBC into treatment of hypertyrosinemia type I (HT I) greatly improved survival by prevention of acute liver failure and hepatocellular carcinoma. However, there are first reports of cognitive impairment in patients with elevated plasma tyrosine concentrations. Methods: We here assess the neurocognitive development using standardized psychometric test batteries with respect to cognition, motor abilities and speech in nine early‐treated patients with HT I under long‐term NTBC treatment. Results: High plasma tyrosine concentrations were frequently documented resulting in elevated 12‐month median plasma tyrosine concentrations in seven out of nine patients. Plasma NTBC concentrations were generally in the lower therapeutic range. Five out of seven patients (71%) above 3 years of age had a total IQ score below the average. In addition, five out of seven patients above 3 years showed an inhomogenous test profile with significant differences between the different testing scales. Motor abilities were subnormal in four out of seven patients(57%). Cerebral MRI revealed no abnormalities. Logopedic evaluation in children at school age documented dysfunction or retardation in language development in all but one of the tested patients (80%), however, all but one patients had a migration background. Conclusions: A high number of patients performed below normal in the assessment of development, motor function and speech. We propose intellectual impairment as long‐term complication in HT type I with elevated plasma tyrosine under NTBC treatment as observed in other hypertyrosinemias. These findings remain to be reproduced in greater patient numbers.