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

Gina A Montoya Parra,Mirjam Kuhn,Anita Macdonald,Aysun Cetinyurek-Yavuz,Rani H Singh

doi:10.1186/s13023-018-0839-x

Gina A Montoya Parra, Mirjam Kuhn + Show 3 more

Open Access

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

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Abstract

BackgroundDespite 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.ResultsOf 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.ConclusionsThe 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.

Highlights

Despite early and ongoing dietary management with a phe-restricted diet, suboptimal neuropsychological function has been observed in PKU
Different hypotheses focusing on the pathogenesis of PKU and disturbed amino acids transport from blood to brain on cerebral neurotransmitter and protein synthesis have been proposed, a detailed examination of this evidence is beyond the scope of this review
We have systematically reviewed, and performed meta-analysis where possible, the nutrient status of Docosahexaenoic acid (DHA), eicosapentanoic acid (EPA), phospholipids, selenium, vitamins B6, B12, E, C, A, D, folic acid, choline, uridine, calcium, magnesium, zinc, iron, iodine and cholesterol that are important for optimal brain function

Summary

Introduction

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. Despite early and continuous low phe dietary management, PKU patients have been shown to have suboptimal neuropsychological function compared to healthy controls, in particular lower IQ, slower information processing [13, 14] and suboptimal executive functioning [15,16,17]. Different hypotheses focusing on the pathogenesis of PKU and disturbed amino acids transport from blood to brain on cerebral neurotransmitter and protein synthesis have been proposed, a detailed examination of this evidence is beyond the scope of this review

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