Abstract
Children with phenylketonuria (PKU) follow a protein restricted diet with negligible amounts of docosahexaenoic acid (DHA). Low DHA intakes might explain subtle neurological deficits in PKU. We studied whether a DHA supply modified plasma DHA and neurological and intellectual functioning in PKU. In a double-blind multicentric trial, 109 PKU patients were randomized to DHA doses from 0 to 7 mg/kg&day for six months. Before and after supplementation, we determined plasma fatty acid concentrations, latencies of visually evoked potentials, fine and gross motor behavior, and IQ. Fatty acid desaturase genotypes were also determined. DHA supplementation increased plasma glycerophospholipid DHA proportional to dose by 0.4% DHA per 1 mg intake/kg bodyweight. Functional outcomes were not associated with DHA status before and after intervention and remained unchanged by supplementation. Genotypes were associated with plasma arachidonic acid levels and, if considered together with the levels of the precursor alpha-linolenic acid, also with DHA. Functional outcomes and supplementation effects were not significantly associated with genotype. DHA intakes up to 7 mg/kg did not improve neurological functions in PKU children. Nervous tissues may be less prone to low DHA levels after infancy, or higher doses might be required to impact neurological functions. In situations of minimal dietary DHA, endogenous synthesis of DHA from alpha-linolenic acid could relevantly contribute to DHA status.
Highlights
Children with classical phenylketonuria (PKU, OMIM 261600) diagnosed by newborn screening who receive adequate dietary treatment from the neonatal age onwards generally reach the normal range of neurological and cognitive functioning, even though some differences in performance when compared to healthy siblings have been demonstrated [1,2]
The lack of significant improvement of neurological and cognitive function in the PKU children is in line with observations in healthy children and adolescents, which often do not report a significant benefit of docosahexaenoic acid (DHA) or fish oil supplementation [26]
Our results indicate that DHA intakes of up to 7 mg/kg&day in PKU children lead to a linear increase of the DHA status, but not to any significant improvement of neurological or cognitive functions
Summary
Children with classical phenylketonuria (PKU, OMIM 261600) diagnosed by newborn screening who receive adequate dietary treatment from the neonatal age onwards generally reach the normal range of neurological and cognitive functioning, even though some differences in performance when compared to healthy siblings have been demonstrated [1,2]. The PKU diet is based on a strictly limited intake of natural protein, supplemented with a phenylalanine (Phe) free amino acid mixture. The PKU diet generally excludes protein rich animal foods, such as dairy products, meat, eggs, and fish, which are natural sources of the long chain polyunsaturated fatty acids (LC-PUFA) [3]. Humans can endogenously produce LC-PUFA from precursor essential fatty acids, but the rate of conversion is limited and dietary intake is the key determinant of blood levels of the n-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA). Children with PKU often have significantly lower blood levels of DHA than healthy controls [4,5,6,7].
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