Objective:

To review performance data on a clinically available biochemical assay designed to aid in the diagnosis of SORD deficiency-related peripheral neuropathy.

Background:

Sorbitol dehydrogenase (SORD) deficiency is a common hereditary form of peripheral neuropathy. Molecular analysis of the SORD gene is technically challenging due to genomic homology and complex structural variation. We developed a novel urine biochemical assay to assist in diagnosing SORD deficiency and present initial clinical findings from the first seven months of testing.

Design/Methods:

A gas chromatography-mass spectrometry method measuring the excretion of sorbitol and xylitol in urine was clinically validated. Prior to the test's launch, we evaluated 21 individuals with confirmed SORD deficiency and 678 unaffected individuals. Since February 2024, urine samples from an additional 274 patients were analyzed.

Results:

Urine sorbitol and xylitol excretion were significantly elevated in 13 individuals in clinical testing (median sorbitol values: 1302 mmol/mol creatinine, assay cutoff <35; median xylitol values: 2105 mmol/mol creatinine, assay cutoff <351). The minimum observed sorbitol and xylitol values in biochemically affected individuals were 548 and 1338 mmol/mol creatinine, respectively, which clearly distinguished these individuals from the rest of the testing cohort. Upon contacting the referring physician, several of these individuals were determined to have a diagnosis of SORD deficiency and a final diagnosis is pending on the remaining individuals. None have shown an alternative diagnosis to date. In the pre-launch cohort, the abnormal excretion of sorbitol and xylitol showed 100% sensitivity and specificity for SORD deficiency.

Conclusions:

These data support the clinical utility of this assay for screening and biochemical confirmation of SORD deficiency. The assay provides a rapid screening test and biochemical confirmation of SORD deficiency-related neuropathy using a non-invasive urine sample.