Status of nutrients important in brain function in phenylketonuria: a systematic review and meta-analysis

Gina A. Montoya ParraEmail author View ORCID ID profile,
Rani H. Singh,
Aysun Cetinyurek-Yavuz,
Mirjam Kuhn and
Anita MacDonald

Orphanet Journal of Rare Diseases201813:101

https://doi.org/10.1186/s13023-018-0839-x

Received: 6 March 2018

Accepted: 5 June 2018

Published: 26 June 2018

Abstract

Background

Despite early and ongoing dietary management with a phe-restricted diet, suboptimal neuropsychological function has been observed in PKU. The restrictive nature of the PKU diet may expose patients to sub-optimal nutritional intake and deficiencies which may impact normal brain function. A systematic review of the published literature was carried out, where possible with meta-analysis, to compare the status of nutrients (Nutrients: DHA, EPA phospholipids, selenium, vitamins B6, B12, E, C, A, D, folic acid, choline, uridine, calcium, magnesium, zinc, iron, iodine and cholesterol) known to be important for brain development and functioning between individuals with PKU and healthy controls.

Results

Of 1534 publications identified, 65 studies met the entry criteria. Significantly lower levels of DHA, EPA and cholesterol were found for PKU patients compared to healthy controls. No significant differences in zinc, vitamins B12, E and D, calcium, iron and magnesium were found between PKU patients and controls. Because of considerable heterogeneity, the meta-analyses findings for folate and selenium were not reported. Due to an insufficient number of publications (< 4) no meta-analysis was undertaken for vitamins A, C and B6, choline, uridine, iodine and phospholipids.

Conclusions

The current data show that PKU patients have lower availability of DHA, EPA and cholesterol. Compliance with the phe-restricted diet including the micronutrient fortified protein substitute (PS) is essential to ensure adequate micronutrient status. Given the complexity of the diet, patients’ micronutrient and fatty acid status should be continuously monitored, with a particular focus on patients who are non-compliant or poorly compliant with their PS. Given their key role in brain function, assessment of the status of nutrients where limited data was found (e.g. choline, iodine) should be undertaken. Standardised reporting of studies in PKU would strengthen the output of meta-analysis and so better inform best practice for this rare condition.

Keywords

Phenylketonuria (PKU)BrainPlasmaNutrientNutritional requirementMetabolismFatty acidsDocosahexaenoic acid (DHA)Eicosapentanoic acid (EPA)Cholesterol, cholineVitaminsMicronutrients, phospholipids, compliance