Background: Children with Zellweger syndrome (ZS), a rare peroxisome deficiency disorder, excrete into the urine highly elevated amounts of urinary metabolites of the arachidonic acid cascade. This pathway may interact in vivo with the L-arginine/nitric oxide (NO) pathway. The aim of this study was to investigate NO production in ZS.
Methods: We studied 11 infants aged 2-12 months with ZS and 30 healthy controls (HC) aged 1-12 months. Urinary excretion of nitrite plus nitrate (U(NO(x))), which is a reliable measure of whole body NO formation, was determined by gas chromatography-mass spectrometry (GC-MS) and corrected for creatinine excretion.
Results: In the subjects aged 1-6 months, U(NO(x)) was more than twofolds higher in ZS (median, 666 micromol/mmol creatinine) as compared to HC (median, 257 micromol/mmol creatinine) (P=0.014 by Mann-Whitney U-test). In children aged 7-12 months, U(NO(x)) was similar for ZS subjects and HC (P=0.96). U(NO(x)) correlated negatively with age in ZS (Kendall's rank correlation coefficient, tau=-0.75, P=0.001). By contrast, no such correlation was found in HC (tau=0.06, P=0.6).
Conclusions: NO production is highly elevated during the first 6 months of life in infants with ZS and falls to normal levels within the following 6 months, suggesting a dramatic decrease in NO synthesis in ZS.