A Rare Type of Polyneuropathy Originating from Mutation in the SORD Gene: A Case Presentation

Background/Purpose: Biallelic mutations in the sorbitol dehydrogenase (SORD) gene have been identified as novel causes of autosomal recessive neuropathies. These alterations lead to dysfunction of sorbitol dehydrogenase, which catalyze the reaction of sorbitol to fructose, and cause intracellular sorbitol accumulation.

Methods: Case presentation: a 17-year-old male patient presented with a first nonfebrile generalized seizure. The clinical examination revealed an unsteady gait, and weakness of the foot lifter on both sides, claw toes, hollow feet, and calf atrophy. Heel gait was not possible, tiptoe gait with help only. Patellar reflex was increased on both sides, and Achilles tendon reflex could not be triggered. The symptoms had been present for several years and were slowly progressive. Walking on uneven ground would be increasingly difficult for the patient. Family history: empty for neurological, neuromuscular diseases.

Results: An EEG showed regular 3/second spike-waves intermittently with age-appropriate background activity. Anticonvulsant medication with valproate and levetiracetam led to seizure freedom, presently. Exome sequencing revealed a homozygous deletion in the SORD gene C.757del, p.(Ala253FINfs*27) in exon 7.

Conclusion: An association between the mutation in the SORD gene and epilepsy has been described in the literature in one case so far. However, with a small number of cases, a causal relationship cannot be excluded with certainty at present. Experimental data suggest a causal therapeutic approach with aldose reductase inhibitors, making SORD mutation a potentially treatable form of neuropathy. The potential for appropriate therapy is being evaluated.

Publication History

Article published online:
28 October 2021