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

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. Hum Mutat 29(4), 532–536, 2008. © 2008 Wiley‐Liss, Inc.