Detection of transaldolase deficiency by quantification of novel seven-carbon chain carbohydrate biomarkers in urine.
Transaldolase deficiency, a recently discovered disorder of carbohydrate metabolism with multisystem involvement, has been diagnosed in 6 patients. Affected patients have abnormal concentrations of polyols in body fluids and in all patients we have previously found increased amounts of a seven-carbon chain carbohydrate which we suspected of being sedoheptulose. We report development of a liquid chromatography-tandem mass spectrometry method for quantitation of the seven-carbon carbohydrates sedoheptulose and mannoheptulose in urine. Additionally, other seven-carbon chain carbohydrates were characterized in urine, including sedoheptitol, perseitol and sedoheptulose 7-phosphate. Transaldolase-deficient patients had significantly increased urinary sedoheptulose and sedoheptulose 7-phosphate, associated with subtle elevations of mannoheptulose, sedoheptitol and perseitol. Our findings reveal novel urinary biomarkers for identification of transaldolase deficiency.
Wamelink
M M
MM
Metabolic Unit, Department of Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. M.Wamelink@vumc.nl
Smith
D E
DE
Jansen
E E
EE
Verhoeven
N M
NM
Struys
E A
EA
Jakobs
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D002239:Carbohydrate Metabolism, Inborn Errors / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000652:urine; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid / Q000592:standards; D005260:Female; D006539:Heptoses / Q000652:urine*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008356:Mannoheptulose / Q000652:urine; D008875:Middle Aged; D012016:Reference Values; D015203:Reproducibility of Results; D013403:Sugar Phosphates / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000592:standards; D014153:Transaldolase / Q000172:deficiency* / Q000235:genetics; D016482:Urinalysis / Q000379:methods* / Q000592:standards
D015415:Biomarkers; D006539:Heptoses; D013403:Sugar Phosphates; C020495:sedoheptulose 7-phosphate; C003011:sedoheptulose; C025642:perseitol; D008356:Mannoheptulose; D014153:Transaldolase