Free asymmetric dimethylarginine (ADMA) is low in children and adolescents with classical phenylketonuria (PKU)

J Inherit Metab Dis. 2012 Sep;35(5):817-21. doi: 10.1007/s10545-011-9448-8. Epub 2012 Jan 31.


Introduction: Free asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide synthases (NOS). Suppression of nitric oxide (NO) synthesis increases the risk of atherosclerosis. Nevertheless, in the condition of oxidative stress, NOS blockade by ADMA may exert protective effects. Protein metabolism is altered in patients with phenylketonuria (PKU) on dietary treatment and as shown recently, oxidative stress is high in PKU. Since free ADMA concentrations are determined by both protein metabolism and oxidative stress we hypothesized, that free ADMA levels may be elevated in PKU patients.

Design: Sixteen patientswith PKU on dietary treatment (mean age 10.1 ± 5.2 yrs), and 91 healthy children (mean age 11.6 ± 3.7 yrs) participated in a cross sectional study.

Results: ADMA, total homocysteine (tHcy) and blood glucose were lower and the L-arginine/ADMA ratio was higher in PKU patients compared to controls. No significant correlation was present between phenylalanine (Phe) concentrations, protein intake, and lipid profile, history of cardiovascular disease or ADMA.

Discussion: In contrast to our hypothesis, ADMAwas lower and the L-arginine/ADMA ratio was higher in PKU patients. Therefore, in PKU patients, the regulating function of ADMA on NO synthesis is altered and may thus contribute to oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Arginine / metabolism
  • Atherosclerosis / blood
  • Atherosclerosis / metabolism
  • Blood Glucose / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / metabolism
  • Child
  • Cross-Sectional Studies
  • Female
  • Homocysteine / blood
  • Homocysteine / metabolism
  • Humans
  • Lipid Metabolism
  • Male
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Oxidative Stress
  • Phenylalanine / blood
  • Phenylalanine / metabolism
  • Phenylketonurias / blood*
  • Phenylketonurias / metabolism*


  • Blood Glucose
  • dimethylarginine
  • Homocysteine
  • Nitric Oxide
  • Phenylalanine
  • Arginine
  • Nitric Oxide Synthase