Cystinosis is an autosomal recessive
lysosomal storage disease caused by mutations in CTNS. The most prevalent CTNS mutation is a homozygous 57-kb deletion that also includes an adjacent gene named SHPK (CARKL), encoding sedoheptulokinase. Patients with this deletion have elevated urinary concentrations of
sedoheptulose. Using derivatisation with pentafluorobenzyl
hydroxylamine and liquid chromatography-tandem mass spectrometry (LC-MS/MS), we developed a new sensitive method for the quantification of
sedoheptulose in dried blood spots. This method can be utilized as a quick screening test to detect
cystinosis patients homozygous for the 57-kb deletion in CTNS; which is the most common mutation of
cystinosis.
Sedoheptulose concentrations in the deleted patients were 6 to 23 times above the upper limit for controls. The assessment of
sedoheptulose in a bloodspot from a known
cystinosis patient homozygous for the 57-kb deletion retrieved from the Dutch neonatal screening program showed that
sedoheptulose was already elevated in the neonatal period. There was no overlap in
sedoheptulose levels between
cystinosis patients homozygous for the 57-kb deletion and
cystinosis patients not homozygous for this deletion. Our presented method can be used prior to mutation analysis to detect
cystinosis patients homozygous for the 57-kb deletion. We feel that the presented method enables fast (pre)-symptomatic detection of
cystinosis patients homozygous for the 57-kb deletion, allowing early treatment.