Prognostic Markers for Phenylketonuria
Research type
Research Study
Full title
Evaluation of current and novel circulating prognostic biomarkers for phenylketonuria
IRAS ID
132727
Contact name
Radha Ramachandran
Contact email
Sponsor organisation
Guys and St Thomas NHS foundation Trust
Research summary
Phenylalainine is an amino acid precursor for tyrosine, which in turn is a precursor synthesis of neurotransmitters like catecholamines and serotonin. Circulating phenylalanine and tyrosine are transported to the brain for synthesis of neurotransmitters. An autosomal recessive defect in the gene encoding the phenylalanine hydroxylase enzyme, results in Phenylketonuria. With an incidence of approximately 1: 10, 000, Phenylketonuria is the most common genetically inherited metabolic disorder in the UK. Patients with phenylketonuria are unable to metabolise phenylalanine. Symptoms are secondary to both accumulation of phenylalanine and toxic its metabolites and due to poor availability of tyrosine leading to suboptimal neurotransmitter synthesis. Untreated, patients develop severe intellectual, behavioural and speech difficulties and almost always need institutionalised care. Treatment, if started in the neonatal period, is successful. It involves lowering circulating phenylalanine levels, using a combination of a very strict low protein diet and supplementation with synthetic phenylalanine free proteins. Good compliance results in excellent outcome, with patients able to lead independent lives in the community. However, it is now increasingly recognised that adult patients often present with varying degrees of problems in mood, executive function and memory despite being on treatment. These symptoms, although more common in patients who have discontinued the diet, do not seem to be related to circulating phenylalanine levels. A significant number of patients with phenylalanine levels in the therapeutic range also experience these problems. This suggests that phenylalanine levels alone are not reflective of the brain function. Our study aims to identify prognostic markers for phenylketonuria by correlating levels of targeted metabolites and proteins in the blood with the clinical features of neuropsychiatric disturbance.
REC name
North West - Preston Research Ethics Committee
REC reference
13/NW/0601
Date of REC Opinion
13 Aug 2013
REC opinion
Favourable Opinion