Executive and social functioning in patients with Tyrosinemia Type 1
Research type
Research Study
Full title
Executive and social functioning in patients with Tyrosinemia Type 1
IRAS ID
150248
Contact name
R. Jahja
Contact email
Sponsor organisation
Univsersity Medical Center Groningen
Duration of Study in the UK
4 years, 0 months, 1 days
Research summary
Patients with Hereditary Tyrosinemia Type 1 (HT1; deficiency of fumarylacetoacetate hydrolase, FAH) usually present with acute liver failure during the first months of life, or (somewhat later) with renal tubular dysfunction with rickets. Originally, HT1 was treated with a tyrosine-phenylalanine restricted diet, usually followed by liver transplantation. Since the discovery of 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione (NTBC), HT1 patients are treated by NTBC and diet with good outcome with regard to liver disease and renal problems. However, during the past years some preliminary evidence has been provided that these patients are at risk of non-optimal neurocognitive outcome. It remains unclear whether these deficits are caused by the disease itself, treatment with NTBC, the resulting high tyrosine, or the low phenylalanine concentrations that are usually seen.
In this observational cross-sectional study, the main objective is to explore the executive, social-cognitive, and social functioning and behaviour of HT1 patients in relation to present and past tyrosine and phenylalanine levels, history of treatment and treatment adherence, and to explore the abovementioned constructs in relation to daily life functioning of HT1 patients.
We estimate that 35 HT1 patients and 35 matched controls from the UK will be tested with a wide range of neuropsychological instruments, including executive functioning, social-cognitive, and social functioning and behaviour. Questionnaires measuring executive and social functioning and behaviour in daily life are also used. Historical and concurrent tyrosine and phenylalanine concentrations are used as predictors expecting significant differences between HT1 patients with high and low blood levels, and between patients and controls.
Bloodspots (three times) and blood samples (once) will be analyzed at the day of testing to discovering fluctuations in present tyrosine and phenylalanine levels. In total the study will last 3-4 hours.
REC name
West Midlands - South Birmingham Research Ethics Committee
REC reference
14/WM/1075
Date of REC Opinion
18 Sep 2014
REC opinion
Further Information Favourable Opinion