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Title: Dietary adherence in phenylketonuria (PKU) and effects on cognitive function and quality of life
Author: Hofman, Denise Leonne
ISNI:       0000 0004 7654 8005
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2018
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Phenylketonuria (PKU) is a rare inherited metabolic disorder, characterised by reduced activity of the hepatic enzyme phenylalanine hydroxylase (PAH). PAH is responsible for the conversion of phenylalanine (Phe) to tyrosine (Tyr). Reduced PAH activity results in elevated Phe levels, decreased Tyr levels and an altered Phe:Tyr ratio. When left untreated, PKU causes severe and irreversible neurological impairments. Although early treatment prevents severe cognitive impairments, deficits in cognitive functioning are still observed. The conventional treatment for PKU is a low-protein (Phe-restricted) diet, supplemented with other amino acids and nutrients lacking in the low-protein diet. Due to the restrictive and complex nature of the dietary management, adherence to the PKU diet is poor in a large proportion of early treated adults with PKU (ET AwPKU), who often follow a self-restricted diet without sufficient supplementation with prescribed protein substitutes. To date, the effects of such dietary practice on nutritional status, quality of life (QoL)/wellbeing and cognitive functioning have not been well documented. Hence, this thesis examines cognitive function and QoL/wellbeing in ET AwPKU in relation to dietary adherence. A systematic review identified 22 articles reporting on outcomes from 16 studies which showed that, despite early treatment, ET AwPKU have deficits in sustained attention, working memory, and motor skills compared to healthy controls. In an online study, ET AwPKU (n=27) showed subtle deficits in episodic memory at a younger age than matched healthy controls (n=28) plus impaired speed of response across a range of cognitive tasks. An online survey examining the factors affecting dietary adherence in English, Dutch and German speaking ET AwPKU (n=71) suggested that poor adherence was associated with previous off-diet behaviour and negative attributes of the prescribed protein substitutes (e.g. bitter (after)taste, convenience). To improve dietary practices of semi-adherent ET AwPKU and assess subsequent effects on nutritional status, QoL/wellbeing and cognitive functioning, a 12-week dietary intervention study with a novel, more palatable, casein glycomacropeptide (CGMP)- based protein substitute was carried out in 10 patients. Improvements in QoL were evident with little effect on nutritional status or cognitive function. This new product could improve adherence to the PKU diet with potential long-term effects on nutritional status, QoL/wellbeing and cognitive function.
Supervisor: Lawton, Clare Louise ; Dye, Louise Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available