Elevated urinary excretion of nitric oxide metabolites in young infants with Zellweger syndrome

Abstract

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 μmol/mmol creatinine) as compared to HC (median, 257 μmol/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, τ=−0.75, P=0.001). By contrast, no such correlation was found in HC ( τ=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.