Stereoselective analysis of 2-hydroxysebacic acid in urine of patients with Zellweger syndrome and of premature infants fed with medium-chain triglycerides

• Published in: Journal of inherited metabolic disease Vol. 26; no. 6; pp. 583 - 592
• Main Authors: MUTH, A, MOSANDL, A, WANDERS, R. J. A, NOWACZYK, M. J. M, BARIC, I, BÖHLES, H, SEWELL, A. C
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.01.2003; Blackwell Publishing Ltd
• Subjects: Biological and medical sciences; Child, Preschool; Chromatography, Gas; Decanoic Acids - urine; Diet; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Humans; Hydroxy Acids - urine; Infant; Infant, Newborn; Infant, Premature - urine; Male; Mass Spectrometry; Molecular and cellular biology; Stereoisomerism; Triglycerides - therapeutic use; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Zellweger Syndrome - diet therapy; Zellweger Syndrome - urine; Human; Premature; Urine; Obesity; Nutrition; Nutrition disorder; Lipids; Patient; Metabolic diseases; Infant; Cerebrohepatorenal syndrome; Medium chain; Triglyceride; Enzymopathy; Genetic disease; Acids; Analysis; Peroxisomal disorders; Genetics; Nutritional status
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1023/A:1025908216639

The chiral metabolite 2-hydroxysebacic acid (2-HS) is considered to be an important diagnostic marker for peroxisomal disorders. The pathway of formation of 2-HS, excreted in increased amounts in patients with peroxisomal diseases, is not absolutely clear. Moreover, there is no information about the enantiomeric distribution of 2-HS in human urine. Here, we describe the stereodifferentiation of 2-HS in urine samples of nine patients with Zellweger syndrome (ZS), and for the first time in urine samples of premature infants fed a medium-chain triglyceride (MCT)-containing diet. Using enantioselective multidimensional gas chromatography-mass spectrometry, an increased excretion of 2R-HS was observed in all investigated ZS patients. 2-HS was also present in urine samples of premature infants fed MCT. Analogously to the ZS patients, a dominant 2R-HS excretion in the urine samples of the premature infants was identified. The formation of 2-HS is expected to result from the same or similar pathways as described for ZS patients. Additionally, we determined the absolute configuration of urinary 3-hydroxysebacic acid (3-HS) in the cases investigated. The enantioselective analysis provides further information for the diagnosis and treatment of patients with impaired peroxisomal fatty acid oxidation. Further insight into the metabolic origin and the biochemical pathway leading to these urinary metabolites is provided.