Measurement of Red Blood Cell Sorbitol Dehydrogenase Activity for Fast Screening of <scp>SORD</scp> ‐Related Neuropathies

BACKGROUND AND AIMS: To develop an assay to measure red blood cell (RBC) sorbitol dehydrogenase (SORD) activity for fast laboratory screening of SORD-related neuropathies, and to provide additional phenotypic arguments in case of ambiguous genetic results. METHODS: . The decrease in absorbance at λ = 340 nm was monitored throughout the course of the reaction. Results were expressed as % activity compared to a within-run control. A cohort of 38 individuals was evaluated over 13 runs: 13 individuals served as within-run controls, 3 were diagnosed with SORD deficiency, 2 were highly suspected of having SORD deficiency, 1 exhibited incidental genomic findings in the SORD gene, and 19 presented with neuropathy or myopathy of undetermined etiology. RESULTS: RBC SORD activity was significantly reduced in individuals diagnosed with SORD deficiency when compared to within-run controls, whereas in contrast, individuals without SORD deficiency did not exhibit this reduction. A comparison of these two groups showed that activities were significantly lower in deficient individuals (p = 0.00006). A test cutoff of < 30% yielded 100% sensitivity and specificity to detect deficient individuals. INTERPRETATION: This test provides a useful alternative to measuring plasma or urine sorbitol with mass spectrometry, allowing clinicians to directly evaluate SORD activity in RBC. As a result, it enables quick and convenient screening for SORD-related neuropathies during standard clinical procedures.