Phenylketonuria: optimizing care

Abstract

Phenylketonuria (PKU; MIM 261600) is an autosomal recessive disorder of phenylalanine metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase (EC 1.14.16.1). PKU leads to severe cognitive impairment due to accumulation of phenylalanine in the brain. Treatment consists of dietary phenylalanine intake restriction (an essential amino acid) through a diet low in natural protein, in order to achieve safe Phe blood levels. The treatment of PKU has been very successful since the introduction of newborn screening in the 1960’s, which has enabled caregivers to identify patients and start dietary natural protein restriction within the first weeks of life. Early and continuous treatment has led to prevention of severe cognitive impairment and near normalization of outcomes. Despite these great achievements the treatment of PKU has also led to some new challenges in patient care. Some of these newly encountered issues may be due to the dietary restrictions, while others may be caused by the disease itself. Optimizing care in patients with PKU needs both fine-tuning of the treatment itself, and evaluation and management of adverse outcomes of the treatment. This thesis presents several studies focussing on the following topics related to optimizing care in PKU: clinical pathways as a tool for multidisciplinary consensus in the care for metabolic disorders; the time burden, out-of-pocket-costs and health related quality of life of patients with PKU; nutrient status and bone health in PKU