Abstract
BackgroundPatients with phenylketonuria (PKU) have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LC-PUFA). Long-chain saturated fatty acids are substrates of mitochondrial fatty acid oxidation for acetyl-CoA production. LC-PUFA are discussed to affect inflammatory and haemostaseological processes in health and disease. The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here.Methodology/Principal Findings12 children with PKU under good metabolic control and 8 healthy controls were included. Activated fatty acids (acylcarnitines C6–C18) in dried blood and the cholesterol metabolism in serum were analyzed by liquid chromatographic tandem mass spectrometry (LC-MS/MS). Fatty acid composition of plasma glycerophospholipids was determined by gas chromatography. LC-PUFA metabolites were analyzed in supernatants by LC-MS/MS before and after platelet activation and aggregation using a standardized protocol. Patients with PKU had significantly lower free carnitine and lower activated fatty acids in dried blood compared to controls. Phytosterols as marker of cholesterol (re-) absorption were not influenced by the dietary fatty acid restriction. Fatty acid composition in glycerophospholipids was comparable to that of healthy controls. However, patients with PKU showed significantly increased concentrations of y-linolenic acid (C18:3n-6) a precursor of arachidonic acid. In the PKU patients significantly higher platelet counts were observed. After activation with collagen platelet aggregation and thromboxane B2 and thromboxane B3 release did not differ from that of healthy controls.Conclusion/SignificanceLong-term dietary fatty acid restriction influenced the intermediates of mitochondrial beta-oxidation. No functional influence on unsaturated fatty acid metabolism and platelet aggregation in patients with PKU was detected.
Highlights
Phenylketonuria (PKU; OMIM 261600) is one of the most common inborn metabolic diseases, approximately affecting one in 8000 newborns in Western Europe [1]
Participants Patients with diagnosed classical PKU were eligible for inclusion if they were under good metabolic control; i.e. a documented average phenylalanine concentration in dried blood spots was below 360 mmol/L for patients,10 years, below 900 mmol/l for patients .10 years, determined at least monthly over the previous six months
Participants 12 (6 females, 6 males) early treated children and adolescents with classical PKU aged 5–14 years and 8 healthy controls (5 females, 3 males) aged 5–17 years were included in the study
Summary
Phenylketonuria (PKU; OMIM 261600) is one of the most common inborn metabolic diseases, approximately affecting one in 8000 newborns in Western Europe [1]. It is caused by deficient activity of phenylalanine hydroxylase. Since protein-rich foods such as meat, milk products, eggs, and fish are the predominant nutritional sources of animal fat, especially of saturated fatty acids and long chain polyunsaturated fatty acids (LC-PUFA), patients with PKU have a low dietary LC-PUFA intake [3,4]. Patients with phenylketonuria (PKU) have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LCPUFA). The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here
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