Elevated urinary excretion of nitric oxide metabolites in young infants with Zellweger syndrome.
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.
Surdacki
Andrzej
A
Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
Tsikas
Dimitrios
D
Mayatepek
Ertan
E
Frölich
Jürgen C
JC
D000375:Aging / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D008297:Male; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000652:urine*; D009573:Nitrites / Q000652:urine; D011786:Quality Control; D012016:Reference Values; D015211:Zellweger Syndrome / Q000652:urine*
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D003404:Creatinine