Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria.

INTRODUCTION: In phenylketonuria (PKU), a natural protein-restricted dietary treatment prevents severe cognitive impairment. Nutrient deficiencies may occur due to strict diet. This study is aimed at evaluating the dietary intake and blood concentrations of micronutrients and essential fatty acids (FA), bone mineral density (BMD) and fracture history in patients on long-term dietary treatment. METHODS: Sixty early diagnosed Dutch patients (aged 1-39 years) were included in a multi-center cross-sectional study. Their dietary intake, blood concentrations of micronutrients, FA, fracture history and BMD were assessed. RESULTS: Selenium dietary intake and serum concentrations were low in 14 and 46% of patients, respectively. The serum 25-OH vitamin D2 + D3 concentration was low in 14% of patients while 20% of patients had a low vitamin D intake. Zinc serum concentrations were below normal in 14% of patients, despite adequate intake. Folic acid serum concentrations and intake were elevated. Despite safe total protein and fat intake, arginine plasma concentrations and erythrocyte eicosapentaenoic acid were below reference values in 19 and 6% of patients, respectively. Low BMD (Z-score <-2) was slightly more prevalent in patients, but the lifetime fracture prevalence was comparable to the general population. CONCLUSIONS: Dutch patients with PKU on long-term dietary treatment have a near normal nutrient status. Supplementation of micronutrients of which deficiency may be deleterious (e.g., vitamin D and selenium) should be considered. BMD warrants further investigation.

High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial.

The main debate in the treatment of Phenylketonuria (PKU) is whether adult patients need the strict phenylalanine (Phe)-restricted diet. Physicians and patients lack evidence-based guidelines to help them make well-informed choices. We have carried out the first randomised double-blind placebo-controlled trial into the effects of short-term elevation of Phe levels on neuropsychological functions and mood of adults with PKU. Nine continuously treated adults with PKU underwent two 4-week supplementation periods: one with Phe, mimicking normal dietary intake, and one with placebo in randomly allocated order via a randomisation coding list in a double-blind cross-over design. A set of neuropsychological tests (Amsterdam Neuropsychological Tasks) was administered at the end of each study period. In addition, patients and for each patient a friend or relative, completed weekly Profile of Mood States (POMS) questionnaires, evaluating the patients' mood. Phe levels were measured twice weekly. Mean plasma Phe levels were significantly higher during Phe supplementation compared with placebo (p = 0.008). Neuropsychological tests demonstrated an impairment in sustained attention during Phe supplementation (p = 0.029). Both patients and their friend or relative reported lower scores on the POMS questionnaires during Phe supplementation (p = 0.017 and p = 0.040, respectively). High plasma Phe levels have a direct negative effect on both sustained attention and on mood in adult patients with PKU. A Phe-restricted "diet for life" might be an advisable option for many.

"MY PKU": increasing self-management in patients with phenylketonuria. A randomized controlled trial.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine metabolism. The inability to convert phenylalanine (Phe) into tyrosine causes Phe to accumulate in the body. Adherence to a protein restricted diet, resulting in reduced Phe levels, is essential to prevent cognitive decline. Frequent evaluation of plasma Phe levels and, if necessary, adjustment of the diet are the mainstay of treatment. We aimed to assess whether increased self-management of PKU patients and/or their parents is feasible and safe, by providing direct online access to blood Phe values without immediate professional guidance. METHODS: Thirty-eight patients aged ≥ 1 year participated in a 10 month randomized controlled trial. Patients were randomized into a study group (1) or a control group (2). Group 2 continued the usual procedure: a phone call or e-mail by a dietician in case of a deviant Phe value. Group 1 was given a personal "My PKU" web page with a graph of their recent and previous Phe values, online general information about the dietary treatment and the Dutch PKU follow-up guidelines, and a message-box to contact their dietician if necessary. Phe values were provided on "My PKU" without advice. Outcome measures were: differences in mean Phe value, percentage of values above the recommended range and Phe sample frequency, between a 10-month pre-study period and the study period in each group, and between the groups in both periods. Furthermore we assessed satisfaction of patients and/or parents with the 'My PKU' procedure of online availability. RESULTS: There were no significant differences in mean Phe value, percentage of values above recommended range or in frequency of blood spot sampling for Phe determination between the pre-study period and the study period in each group, nor between the 2 groups during the periods. All patients and/or parents expressed a high level of satisfaction with the new way of disease management. CONCLUSIONS: Increased self-management in PKU by providing patients and/or parents their Phe values without advice is feasible and safe and is highly appreciated. TRIAL REGISTRATION: The trial was registered with The Netherlands National Trial Register (NTR #1171) before recruitment of patients.