Carnitine Status in Early-Treated Children, Adolescents and Young Adults with Phenylketonuria on Low Phenylalanine Diets

Abstract

Background: In patients with phenylketonuria (PKU), the carnitine status may be impaired for metabolic or dietary reasons, including low carnitine intake, a deficient synthesis and acylcarnitine production from phenylalanine (Phe) metabolites. Methods: Free carnitine and acylcarnitine status was assessed in 30 PKU patients, aged 0.5–36 years, mean age 13.8 years. Our cohort was divided into 2 groups according to the preparations of Phe-free amino acids (AA) prescribed, with or without carnitine supplementation. Daily Phe intake, dosage of AA mixtures and body weight were recorded along with measurements of acylcarnitines in blood spots (by tandem mass spectrometry) and serum AA. Control data were obtained from 50 healthy volunteers (aged 0.2–39 years, mean age 14.2. years). Statistical analysis comprised the t test, ANOVA and Pearson’s correlation. Results: PKU patients had lower free carnitine (C0) concentrations than controls (25.82 ± 7.38 vs. 31.28 ± 6.17 µmol/l; p < 0.001) and lower octanoyl- and decanoylcarnitine. Mean C0 and acylcarnitine concentrations did not differ between PKU patients taking the various protein substitutes with or without carnitine; mean C0 levels in PKU patients receiving AA enriched with carnitine were still lower compared with controls (p < 0.05). Conclusions: Actual dietary regimens can not completely normalize the carnitine status; therefore, carnitine levels should be given careful consideration in subjects with PKU.

Dietary Habits and Metabolic Control in Adolescents and Young Adults with Phenylketonuria: Self-Imposed Protein Restriction May Be Harmful

“…This does not completely rule out deficiencies in tissues. In previous studies on treated PKU patients, vitamin deficiencies (Hoeks et al 2009) and low normal free carnitine values (Weigel et al 2008) were found. An increased risk of vitamin B12-deficiency was reported in PKU patients on a relaxed diet in a previous study (Robinson et al 2000); as methylmalonic acid in urine was negative, vitamin B12-deficiency could be ruled out in our cohort.…”

Evaluation of Plasma Trace Element and Mineral Status in Children and Adolescents with Phenylketonuria Using Data from Inductively-Coupled-Plasma Atomic Emission and Mass Spectrometric Analysis

“…Patients with blood Phe concentrations >600 μmol/l, who had normal urinary pterins and normal blood dihydropteridine reductase activity and were found to be unresponsive to BH4, were put on a dietary regimen. Further clinical and biochemical details of our cohort have been published previously [6]. A low-Phe diet was carefully adjusted according to individual blood Phe levels; all patients were treated with standard Phe-free protein substitutes enriched with other micronutrients such as vitamins and minerals.…”

“…Acrodermatitis enteropathica-like eruptions have been noted in individuals with various metabolic disorders, including inborn errors of amino acid metabolism [5]. We have also shown that other co-factors in metabolism, such as carnitine, can also be impaired in PKU patients for metabolic or dietary reasons [6]. In addition, oxidative stress is a concern in patients with PKU [7].…”

Inborn Errors of Metabolism and Brain Involvement - 5 Years Experience from a Tertiary Care Center in South India

“…The same carrier transports phenylalanine as well as large neutral amino acids into the brain; hence their use diminishes toxicity due to phenylalanine. Weigel et al (2008) report low free carnitine levels in PKU patients given low phenylalanine diet. They suggest that carnitine level should be monitored in PKU patients.…”