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

Hum Mutat. 2008 Apr;29(4):532-6. doi: 10.1002/humu.20685.


The most common mutation in the nephropathic cystinosis (CTNS) gene is a homozygous 57-kb deletion that also includes an adjacent gene carbohydrate kinase-like (CARKL). The latter gene encodes a protein that is predicted to function as a carbohydrate kinase. Cystinosis patients with the common 57-kb deletion had strongly elevated urinary concentrations of sedoheptulose (28-451 mmol/mol creatinine; controls and other cystinosis patients <9) and erythritol (234-1110 mmol/mol creatinine; controls and other cystinosis patients <148). Enzyme studies performed on fibroblast homogenates derived from patients carrying the 57-kb deletion revealed 80% reduction in their sedoheptulose phosphorylating activity compared to cystinosis patients with other mutations and controls. This indicates that the CARKL-encoded protein, sedoheptulokinase (SHK), is responsible for the reaction: sedoheptulose + ATP --> sedoheptulose-7-phosphate + ADP and that deletion of CARKL causes urinary accumulation of sedoheptulose and erythritol.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Transport Systems, Neutral / deficiency
  • Amino Acid Transport Systems, Neutral / genetics
  • Case-Control Studies
  • Child
  • Chromosome Mapping
  • Cystinosis / enzymology*
  • Cystinosis / genetics*
  • Cystinosis / urine
  • Erythritol / urine
  • Fibroblasts / enzymology
  • Genes, Recessive
  • Heptoses / urine*
  • Humans
  • Infant
  • Models, Biological
  • Pentose Phosphate Pathway
  • Phosphotransferases (Alcohol Group Acceptor)
  • Phosphotransferases / deficiency*
  • Phosphotransferases / genetics*
  • Sequence Deletion
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics*


  • Amino Acid Transport Systems, Neutral
  • CTNS protein, human
  • Heptoses
  • Transcription Factors
  • sedoheptulose
  • Phosphotransferases
  • Phosphotransferases (Alcohol Group Acceptor)
  • SHPK protein, human
  • Erythritol