Measurement of Red Blood Cell Sorbitol Dehydrogenase Activity for Fast Screening of SORD-Related Neuropathies

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.

Hemolysates were incubated in the presence of fructose and NADH to produce sorbitol and NAD⁺. 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.

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.

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.