23 September 2020
A way forward for diabetic neuropathy
Published online 4 May 2020
Research into inherited neuropathies could improve understanding of a diabetes complication.
A study of an inherited peripheral nerve disease reveals a toxic effect of sorbitol accumulation on nerve fibres. This could lead to further insights into diabetic neuropathy, a long-term complication affecting as many as 50% of people with diabetes. It involves nerve damage in the legs and feet and has no effective treatment.
Studies have so far suggested an increased flux through the polyol pathway — a two-step process involving the conversion of glucose to sorbitol, and then to fructose — could be an important marker of diabetic neuropathy. How this leads to nerve damage, however, has been unclear.
Now, scientists report that biallelic mutations (i.e. mutations inherited from both parents) in a gene called sorbitol dehydrogenase (SORD) are associated with the most common form of hereditary neuropathy, known as Charcot–Marie–Tooth (CMT) syndrome, a disease leading to muscle wasting and sensory loss. SORD codes for the SORD enzyme, which is responsible for converting sorbitol to fructose.
The identification of SORD deficiency as the cause of CMT syndrome provides genetic evidence of the neurotoxic effect of sorbitol on peripheral nerves, explains Andrea Cortese of University College London Queen Square Institute of Neurology, in the UK.
The research team, which included scientists in Egypt, Kuwait and Saudi Arabia, analysed a large pool of genetic data collected from more than 1,100 patients with CMT, and found 45 people from 38 families across diverse nationalities carrying the biallelic mutation in SORD.
“We predict our findings will lead to a re-evaluation of the diabetic neuropathy pathophysiology and to a deeper understanding of potential therapeutic strategies for this common disorder,” says Cortese.
Cortese, A. et al. Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Nat. Genet. https://doi.org/10.1038/s41588-020-0615-4 (2020).