Long-chain polyunsaturated fatty acid status in children, adolescents and adults with phenylketonuria

Gramer, Gwendolyn; Haege, Gisela; Langhans, Claus-Dieter; Schuhmann, Vera; Burgard, Peter; Hoffmann, Georg F.

doi:10.1016/j.plefa.2016.04.005

Cited by 11 publications

(11 citation statements)

References 38 publications

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“…Our data confirm previous findings that PKU patients show lower n -3 LC-PUFA than healthy controls, but the differences between healthy omnivorous children and the PKU patients were small in some centres. The DHA data from Istanbul, Santander, and Milan confirm the findings of the 2013 Lohner review [7], while German and UK sites support recent observations from a German PKU study that there was no significant difference between patients and controls [37].…”

Section: Discussionsupporting

confidence: 78%

Determinants of Plasma Docosahexaenoic Acid Levels and Their Relationship to Neurological and Cognitive Functions in PKU Patients: A Double Blind Randomized Supplementation Study

et al. 2018

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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.

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Section: Discussionsupporting

confidence: 78%

Determinants of Plasma Docosahexaenoic Acid Levels and Their Relationship to Neurological and Cognitive Functions in PKU Patients: A Double Blind Randomized Supplementation Study

et al. 2018

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“…We did not find any correlation between daily FAs intake and their serum levels. PUFAs intake did not affect their levels in a study by Gramer and coworkers either (Gramer et al, 2016). The authors noted that DHA levels were similar in patients consuming PKU formula with or without PUFA supplementation.…”

Section: Discussionmentioning

confidence: 84%

“…The PKU diet excludes meat and fish, which are natural sources of long-chain polyunsaturated fatty acids (PUFA) (Al Hafid & Christodoulou, 2015;Singh et al, 2016). PUFA deficiency may negatively impact patients' psychomotor development and may induce metabolic imbalance, thus leading to changes in the fatty acids' (FA) profile (Al Hafid & Christodoulou, 2015;Gramer et al, 2016;Schindeler et al, 2007). It should be noted that information on the relationship between the low-Phe diet and PUFA profile in PKU is contradictory (Acosta et al, 2001;Giovannini et al, 2011;Htun et al, 2015;Lage et al, 2010;van Gool CJ et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Deficiency of long-chain polyunsaturated fatty acids in phenylketonuria: a cross-sectional study

Drzymała-Czyż

Kałużny

Krzyżanowska-Jankowska

et al. 2018

Acta Biochim Pol

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The etiology of altered blood fatty acid (FA) profile in phenylketonuria (PKU) is understood only partially. We aimed to determine whether FAs deficiency is dependent on the diet or metabolic disturbances. The study comprised 40 PKU patients (20 female, 20 male; aged 11 to 35 years; 12 children and 28 adults) and 40 healthy subjects (HS; 20 female, 20 male, aged 18 to 33 years). We assessed the profile of FAs (gas chromatography/mass spectrometry) and analyzed the 72-hour dietary recalls. The amount of C14:0, C16:0 and C16:1n-7, C18:1n-9 did not differ between the analyzed groups. The percentage of C18:0 was higher, while C20:3n-9, C18:2n-6, C20:2n-6, C20:4n-6, C22:4n-6, C22:5n-6 and C22:6n-3 was lower in PKU than in HS. However, C18:3n-6, C18:3n-3 and n-6/n-3 ratio were higher in PKU patients. The C20:4n-6/C20:3n-6 ratio (reaction catalyzed by Δ5-desaturase), the C22:5n-6/C22:4n-6 and the C22:6n-3/C22:5n-3 ratio (both reactions catalyzed by Δ6 desaturase) were significantly lower in PKU patients. Therefore, the deficiency of long-chain polyunsaturated fatty acids in PKU patients may result not only from inadequate supply but also from metabolic disturbances.

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“…As there have been many studies that have reported poor fatty acids status of PKU patients over the last 20 yrs, dietary advice has been modified and some PS have since been fortified with DHA, EPA and the parent essential fatty acids. Interestingly, some recent studies [ 52 – 54 ], where a few or all the patients were taking a fortified PS (essential or long chain n-3 fatty acids) or a modified fat diet, found no difference in DHA and EPA status in PKU patients compared to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

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

Montoya

Singh

Cetinyurek-Yavuz

et al. 2018

Orphanet J Rare Dis

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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.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0839-x) contains supplementary material, which is available to authorized users.

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Long-chain polyunsaturated fatty acid status in children, adolescents and adults with phenylketonuria

Cited by 11 publications

References 38 publications

Determinants of Plasma Docosahexaenoic Acid Levels and Their Relationship to Neurological and Cognitive Functions in PKU Patients: A Double Blind Randomized Supplementation Study

Determinants of Plasma Docosahexaenoic Acid Levels and Their Relationship to Neurological and Cognitive Functions in PKU Patients: A Double Blind Randomized Supplementation Study

Deficiency of long-chain polyunsaturated fatty acids in phenylketonuria: a cross-sectional study

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

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