Detection of transaldolase deficiency by quantification of novel seven‐carbon chain carbohydrate biomarkers in urine

Abstract

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.

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.…”

Transaldolase Deficiency: A New Case Expands the Phenotypic Spectrum

“…TALDO interconverts a three-carbon moiety between different sugars; thus, it enables the production of fructose-6-phosphate and erythrose-4-phosphate from glyceraldehyde-3-phosphate and sedoheptulose-7-phosphate. In the absence of transaldolase intermediate products such as ribitol, D-arabitol and erythritol may accumulate, and their abnormal elevated concentrations can be measured directly (Wamelink et al 2007). Although the diagnosis is rare, the description of more cases is needed for further delineation of the enzyme's deficiency.…”

Clinical, biochemical, and molecular overview of transaldolase deficiency and evaluation of the endocrine function: update of 34 patients

“…Sugars and polyols were measured in urine and/or plasma by gas chromatography (GC) (Jansen et al 1986); the sevencarbon sugars were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) (Wamelink et al 2007). …”