Executive and social functioning in patients with Tyrosinemia Type 1.

Ginkel, W.G. van (Wiggert) (2014) Executive and social functioning in patients with Tyrosinemia Type 1. thesis, Medicine.

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Abstract

Tyrosinemia Type 1 (HT1) is an inborn error of metabolism, in which tyrosine cannot be degraded normally. Instead, the toxic metabolites fumarylaceatoacetate and succinylacetoacetate are accumulating, causing liver failure or renal failure early in life and somewhat later the formation of hepatocellular carcinoma. In the past, a tyrosine and phenylalanine (the precursor of tyrosine) restricted diet was the only possible treatment strategy, eventually followed by liver transplantation when hepatocellular carcinoma was present. Besides their diet, since 1992, HT1 patients are treated with a new compound, called NTBC. NTBC is a herbicide which blocks the conversion of tyrosine at an earlier step, so that the toxic metabolites cannot be formed anymore. Due to NTBC, initial liver and renal problems resolved, the incidence of hepatocellular carcinoma dramatically decreased, and life time expectancy increased. So, it seems that there are no problems anymore. However, in the last few years, some articles have suggested a non-optimal neurocognitive outcome in HT1 patients. This story resembles the story of Phenylketonuria (PKU). PKU is also an inborn error of metabolism, but in this disease phenylalanine cannot be converted into tyrosine. Without early treatment this leads to severe mental retardation, seizures and behavioural problems. Early and adequate phenylalanine restricted dietary treatment prevents patients from mental retardation and all problems seem to be solved. However, after a few years the first articles have arisen showing an impaired neurocognitive outcome despite the dietary treatment. To be able to learn from the experiences in PKU, in the current study, neurocognitive functioning of HT1 patients was compared to the neurocognitive functioning of PKU patients and healthy controls. Several neuropsychological domains were investigated, namely executive functioning, social cognition and behaviour. Besides that, quality of life was also examined. To measure this, we used several validated questionnaires and a computerized test battery, the Amsterdam Neuropsychological tasks. The results show clear impairments on almost all measured neurocognitive domains for HT1 patients. Sometimes the neuropsychological profile of HT1 patients resembles the profile seen in PKU patients. However, in general, HT1 patients seem to be more affected than PKU patients. Furthermore, transplanted patients seem to perform better than patients treated with NTBC and diet. Further research is necessary to compare different HT1 patient groups based on different diagnostic timelines and treatment strategies. Also, more precise neuropsychological research especially focussing on the deficiencies shown in this project is necessary. Furthermore, biochemical causes for this neuropsychological dysfunction could be investigated in a HT1 mice model, already know in literature.

Item Type:	Thesis (Thesis)
Supervisor name:	Spronsen, Prof. Dr. F.J. (Francjan) van
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:53
Last Modified:	25 Jun 2020 10:53
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1379

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