Analysis of polyols in urine by liquid chromatography–tandem mass spectrometry: A useful tool for recognition of inborn errors affecting polyol metabolism

Abstract

Several inborn errors of metabolism with abnormal polyol concentrations in body fluids are known to date. Most of these defects can be diagnosed by the assessment of urinary concentrations of polyols. We present two methods using tandem mass spectrometry for screening for inborn errors affecting polyol metabolism. Urine samples supplemented with internal standards ([13C4]erythritol, [13C2]arabitol and [2H3]sorbitol) were desalted by a mixed-bed ion-exchange resin. Separation was achieved by two different columns. Sugar isomers could not be separated using a Prevail Carbohydrate ES 54 column (method 1), whereas with the other column (Aminex HPX-87C) separation of the isomers was achieved (method 2). Multiple reaction monitoring polyol detection was achieved by tandem mass spectrometry with an electron ion-spray source operating in the negative mode. Age-related reference ranges of polyols (erythritol, treitol, arabitol, ribitol, xylitol, galactitol, mannitol, sorbitol, sedoheptitol and perseitol) in urine were established. The applicability of the method was demonstrated by the abnormal polyol concentrations observed in patients with transaldolase deficiency, ribose-5-phosphate isomerase deficiency and classical galactosaemia. This paper describes two methods for the analysis of urinary polyols by liquid chromatography-tandem mass spectrometry. Method 1 is a fast screening method with the quantification of total isomers and method 2 is a more selective method with the separate quantification of the polyols. Both methods can be used for diagnosing inborn errors of metabolism affecting polyol metabolism.

Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of theCARKLgene

“…Accumulation of sedoheptulose and erythritol has also been found in transaldolase deficiency, an inborn error of the PPP [Wamelink et al, 2005a[Wamelink et al, , 2007. The key clinical findings in transaldolase deficiency include dysmorphic features, with hirsutism, cutis laxa, and antimongoloid slants, hepatosplenomegaly and hepatic fibrosis, thrombocytopenia, and hemolytic anemia with elevated schistocytes, as well as renal (nephrocalcinosis) and cardiac abnormalities [Verhoeven et al, 2001[Verhoeven et al, , 2005 We have identified the function of the CARKL gene: it is responsible for the phosphorylation of sedoheptulose to sedoheptulose monophosphate.…”

“…Erythritol and sedoheptulose were quantified in urine from 10 nephropathic cystinosis patients by liquid chromatography with tandem mass spectrometry (LC-MS/MS) as described [Wamelink et al, 2005a[Wamelink et al, , 2007.…”

Urinary Excretion of Pentose Phosphate Pathway-Associated Polyols in Early Postnatal Life

“…In most previous studies, a rather extended spectrum of polyols has been analyzed [1,[10][11][12] . The present study focused on the four primary pentose phosphate pathwayassociated polyols, which are elevated in ribose 5-phosphate isomerase and transaldolase deficiency, in order to provide a basis for a rational interpretation of pentose phosphate pathway-associated polyol profiles in neonates.…”

“…erythritol, treitol, ribitol, arabitol) with age suggesting an age-dependence for polyol formation [1,10] . In addition, a few studies on polyol profiles during fetal development showed that the concentrations of most of the investigated polyols (inositol, D -sorbitol, erythritol, ribitol) were significantly higher in amniotic fluid than in maternal plasma [11,12] .…”

The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency

“…Calibrators of arabitol, ribitol, xylitol, galactitol, and sorbitol were included in each batch of samples and were processed as described above. LC-MS/MS analysis for quantification of polyols was carried out as described earlier [17].…”