JIMD Reports, Volume 40

Helen Walker, Mervi Pitkanen, Yusof Rahman, Sally F. Barrington, Walker, Helen, Pitkanen, Mervi, Rahman, Yusof, Barrington, Sally F.

To examine neuropsychiatric outcomes in adults with hereditary tyrosinaemia type I (HT-1), treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) and correlate these with functional imaging as well as with tyrosine and phenylalanine-tyrosine (Phe:Tyr) ratios. We retrospectively reviewed the medical records of three adult HT-1 patients with a particular focus on their FDG PET/CT brain scans, neuropsychiatric assessment (including neurocognitive assessment and mood and anxiety ratings) as well as mean tyrosine and phenylalanine levels and Phe:Tyr ratios for 3-month period. The patients had been referred to a specialist joint inherited metabolic disorder and neuropsychiatry clinic. They were all on NTBC; two since 6 weeks of age, and one since 9 years of age. All patients performed below the expectation on the formal neurocognitive testing and had raised plasma tyrosine levels and reduced plasma Phe:Tyr ratios. FDG PET/CT-brain scans were normal in two patients and the third patient (treated with NTBC from 6 weeks) had reduced metabolism in temporal and medial frontal areas bilaterally which correlated with the neurocognitive performance. All three HT-1 patients treated with NTBC had high tyrosine levels, reduced Phe:Tyr ratios and underperformed in neurocognitive testing regardless of the point when the NTBC was first started. One had imaging abnormalities which also correlated with neurocognitive performance. The patient who struggled the most in neurocognitive testing had the highest average plasma tyrosine levels and the lowest Phe:Tyr ratio. Overall, these cases appear to support the previous hypothesis that either the high tyrosine levels or abnormal phenylalanine hydroxylase (PAH) function may well be the causative factor for poor neurocognitive performance. Further systematic, multi-centre studies with a longer follow-up are required to further clarify the relationship between HT-1, NTBC treatment, tyrosine and phenylalanine levels and neurocognitive outcomes.