linoleic-acid and Phenylketonurias

It has been reported that children with classical phenylketonuria (PKU) have reduced levels of arachidonic acid (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3) in plasma and membrane phospholipids compared to controls and may therefore require supplementation. However, it is not established that these changes are specific for PKU. They may as well be attributed to the specific composition of a largely vegetarian diet used for dietary PKU treatment. We therefore investigated the fatty acid composition of plasma phospholipids (PL), plasma cholesterol esters (CE), red blood cell phosphatidylcholine (PC), and red blood cell phosphatidylethanolamine (PE) in two groups of PKU patients including 8 children between 1 and 6 years (group A), 9 adolescents between 11 and 18 years (group B), and 20 age-matched healthy controls. Group A had good dietary control (median plasma phenylalanine 272 mumol/L during the last 6 months before phospholipid analysis) while median phenylalanine in group B was 714 mumol/L (p < 0.001). When compared to age-matched controls, group A showed significantly lower DHA levels in PE (4.21 vs 5.85 weight% (wt%), p < 0.01), in PC (1.02 vs 1.25 wt%, p < 0.05) and in CE (0.25 vs 0.54 wt%, p < 0.05). There was no significant difference of DHA between group B and controls. AA levels were similar in phospholipids of all groups. We conclude that reduced levels of long-chain polyunsaturated fatty acids in PKU patients occur only in those patients with strict dietary therapy with respect to n-3 fatty acids, most probably caused by reduced intake of n-3 fatty acids.

Topics: Adolescent; Child; Child, Preschool; Eating; Erythrocyte Membrane; Erythrocytes; Fatty Acids, Unsaturated; Humans; Infant; Linoleic Acid; Membrane Lipids; Phenylketonurias; Phospholipids

Neonates need arachidonic acid (AA) for their growing tissues, but it is unknown to what extent they can synthesize AA from dietary linoleic acid (LA). We studied infantile AA synthesis by using different natural 13C amounts in dietary fats. The diets of four infants ages 18 +/- 4 days (mean +/- SD) with newly diagnosed phenylketonuria were changed from breast milk or formula to a phenylalanine-free diet with corn oil as the only fat source. Compared with most dietary fats in Europe derived from C3 plants, corn oil LA has a higher 13C content. We determined the 13C content of LA and AA in 0.25-0.5 ml serum before and for 3-4 days after the diet change with gas chromatography combustion isotope ratio mass spectrometry (GC-IRMS). Baseline delta 13C values were -31.5 +/- 1.1% (mean +/- SD) for serum LA and -30.1 +/- 1.2% for AA. The corn oil diet induced changes of delta 13C values over baseline in LA of 8.9 +/- 1.0 on day 1 and 12.7 +/- 0.7 on day 4, respectively. The changes of AA delta 13C values were 0.5 +/- 0.7 and 2.7 +/- 0.7 on days 1 and 4. We conclude that reproducible detection of differences in delta 13C values of fatty acids in small samples of infantile serum, induced by dietary variation of natural 13C amounts, is feasible with GC-IRMS. Since the corn oil diet did not contain AA, the observed change of AA delta 13C shows active endogenous AA synthesis in full-term neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arachidonic Acids; Carbon; Carbon Isotopes; Corn Oil; Dietary Fats; Fatty Acids; Gas Chromatography-Mass Spectrometry; Humans; Infant, Newborn; Linoleic Acid; Linoleic Acids; Milk, Human; Phenylketonurias