SORD deficiency: a plain-language guide

SORD deficiency is an inherited condition in which a missing enzyme allows a sugar called sorbitol to build up in the body, slowly damaging the nerves that control the muscles of the lower legs and feet [1,3].

This page provides general information. It does not replace advice from a doctor or another qualified healthcare professional.

Key facts

• SORD deficiency was only identified as a distinct cause of nerve damage in 2020, so many people living with it have spent years with an unexplained diagnosis [1,17].
• It is also called CMT-SORD, sorbitol dehydrogenase deficiency with peripheral neuropathy, and SORDD. It is counted as a form of Charcot-Marie-Tooth disease type 2 or of distal hereditary motor neuropathy [2,3,4].
• A person can have had genetic testing in the past that came back clear and still have SORD deficiency, because the SORD gene sits beside an almost identical non-working copy that many older tests could not tell apart [1,7,10].
• Sorbitol can be measured in blood or urine, which makes SORD deficiency one of the few inherited nerve conditions with a chemical test that supports the diagnosis [2,5,6].
• Prevalence figures are uncertain. Estimates come from counting a common gene variant in reference populations and from cohorts of people already referred with suspected inherited neuropathy, not from counting cases in the general population [1,2,8,9].
• As of August 2026 there is no approved treatment that slows or reverses SORD deficiency anywhere in the world. Care focuses on strength, walking, foot support and pain [4,12,18].

On this page

• What is SORD deficiency?
• How common is it?
• What causes it?
• What are the symptoms?
• How is it diagnosed?
• How is it treated?
• Living with SORD deficiency
• Thinking about a clinical trial?
• Current research
• Support and further information
• Questions people often ask

What is SORD deficiency?

The nerves running from the spinal cord out to the arms and legs are the peripheral nerves. They carry instructions from the brain to the muscles, and sensations back again [12,13].

Inside cells, the body turns glucose, the main sugar in blood, into a substance called sorbitol, then turns sorbitol into fructose. The enzyme doing that second step is sorbitol dehydrogenase, and the instructions for making it come from a gene called SORD, a gene being a set of instructions inside cells [1,3].

In SORD deficiency both copies of SORD carry a change that stops the enzyme working, so sorbitol builds up in cells and in the blood [1]. Over years this appears to harm the long nerve fibers reaching the feet, which lose the ability to drive the muscles properly [1,15].

Other names. SORD deficiency, sorbitol dehydrogenase deficiency with peripheral neuropathy, SORDD and CMT-SORD all mean the same thing [3,4]. Charcot-Marie-Tooth disease, shortened to CMT, is the umbrella name for inherited conditions damaging the peripheral nerves, and SORD deficiency is one type, usually diagnosed first as Charcot-Marie-Tooth disease type 2 or distal hereditary motor neuropathy [2,12,21].

Diabetic nerve damage looks similar and involves the same sugar pathway, though it follows long-term high blood sugar rather than an inherited change [1,13].

How common is it?

Nobody has counted how many people have SORD deficiency, and each estimate below counts something different.

The most common faulty version of the gene, c.757delG, is carried in a single copy by roughly 3 in every 1,000 people in reference databases, and from that the team who identified the condition calculated that about 1 in 100,000 people would carry two copies of it [1]. Using the same method, later groups estimated at least 3,000 people in the United States [2] and roughly 10,000 across North America and Europe [15]. Those are calculations from gene frequencies, not head counts.

The other kind of estimate comes from testing people already referred to specialist clinics with an unexplained inherited neuropathy. SORD deficiency accounted for up to about 10 percent of those cases in the original study, and 3 to 7 percent in later cohorts in China and Germany [1,8,9]. Those percentages are not population rates. They describe an already-selected group. Reliable figures for Africa, South America, the Middle East and most of Asia are not available, and the true number is very likely higher, since the condition was unknown before 2020 [1,2,17].

What causes it?

SORD deficiency is caused by changes in both copies of the SORD gene [1,3].

People carry two copies of most genes, one from each parent. A condition is autosomal recessive when it appears only if both copies carry a change. Someone with a change in one copy is a carrier: usually healthy, and not affected [4]. Where both parents are carriers, each pregnancy carries about a 1 in 4 chance.

Most people with SORD deficiency are the first in their family to have a nerve condition, and 69 percent of cases in the original study had no family history at all [1]. Its absence is no reason to rule the diagnosis out [4].

The most common change, c.757delG, removes a single letter from the gene instructions, and others have been reported, mostly in single families [1,2,22]. It is present from birth, even though symptoms appear years later [3].

What are the symptoms?

Symptoms usually start in the teenage years, though onset in early childhood and in adulthood are both described, and progression is slow, over decades rather than months [2,3].

The usual pattern is weakness and thinning of the muscles furthest from the trunk, mainly in the lower legs and feet [3]. Common features include [2,3,6]:

• difficulty lifting the front of the foot, causing tripping and a high-stepping walk
• weakness pushing off through the foot
• high-arched feet and curled toes, in 79 percent of people in the largest study
• reduced feeling in the feet, usually milder than the weakness
• weakness in the hands, in about half of one European group
• balance problems and difficulty running, often noticed at school

Nerve tests point to damage to the nerve fiber itself rather than its insulating coating, and motor nerves are affected more than sensory nerves [2,15]. Severity varies: most people in published groups were mild or moderate, about a quarter used ankle and foot supports from their thirties, and most still walked independently later in life [2,6].

When to contact a doctor. SORD deficiency is not known to cause sudden emergencies. Weakness worsening over days or weeks rather than years is not the usual pattern and should be discussed with a doctor promptly, since a different and sometimes treatable condition may be involved [12,13].

How is it diagnosed?

Diagnosis is usually made by a neurologist, a doctor who specializes in nerve conditions, often at a neuromuscular center [4,12]. Several steps are involved:

• Examination and history, looking at walking, foot shape, strength and feeling [4].
• Nerve conduction studies, where small electrical pulses measure how well signals travel along the nerves. In SORD deficiency they show damage to the nerve fibers, mostly the motor ones [2].
• Measuring sorbitol, which in blood is markedly raised, around 22 times higher than in unaffected people in one European group [6]. A newer urine test measures sorbitol with a second substance, xylitol [5]. Specialist laboratories offer both [4,17].
• Genetic testing of the SORD gene, to confirm changes in both copies [2,4].

Why earlier genetic testing can have missed it. Next to the SORD gene sits a second, almost identical stretch of DNA called SORD2P. It is a pseudogene, meaning a broken copy that makes no working enzyme. Standard genetic tests read DNA in short pieces, and short pieces from SORD and SORD2P look so alike that laboratories often could not tell which one they came from. Some panels left the region out altogether for that reason [1,7,10]. Laboratories now use methods designed to read SORD while excluding its look-alike copy [7], and reading DNA in much longer pieces, called long-read sequencing, can also separate them [10]. One reported case shows the effect: a man whose leg weakness began in his twenties had panel testing that found nothing, and was diagnosed only at 72, after whole-genome sequencing and a very high sorbitol level [14].

There is a further reason for missed results. Whole sections of SORD and SORD2P can swap places, an arrangement called an inversion that short-read testing does not see, found in 13 of 151 people with SORD-related neuropathy in one analysis [11]. That work is a preprint, shared publicly but not yet reviewed by other scientists, so treat it as promising rather than settled.

A clear result from a test done before 2020, or from a panel that did not handle the look-alike copy, does not rule out SORD deficiency [4,5].

How is it treated?

There is no approved treatment anywhere that slows or reverses SORD deficiency, and no cure [4,12,18]. Care aims to keep people walking and independent, and good management does improve movement [4,21]:

• Physical and occupational therapy, for strength, flexibility, balance and hand function [4].
• Ankle and foot supports, called ankle-foot orthoses, which hold the foot in a better position and reduce tripping. About a quarter of people in the largest study used them, most from their thirties [2,4].
• Staying active, with guidance from a therapist who knows nerve conditions, and foot or ankle surgery where deformity cannot be managed otherwise [4].
• Pain treatment where nerve pain is present, using medicines developed for nerve pain rather than ordinary painkillers [13,20].
• Regular review at a center used to inherited neuropathies, which is how people hear about research [4,20].

Availability differs between countries: specialist centers, orthotics services and sorbitol testing are established in parts of North America, Europe, Australia and East Asia, and limited or absent elsewhere [2,4].

Living with SORD deficiency

Most people stay under a neurologist or neuromuscular team long term, with therapy and orthotics reviewed as things change [4,20]. Small practical things carry weight: footwear that fits over supports, daily foot checks, since reduced feeling can hide a blister or cut, and handrails where balance is a problem [13]. At school or work, useful adjustments include seating that reduces long standing and help with fine hand tasks [4,12].

A genetics service can explain inheritance for a particular family. No published evidence indicates that SORD deficiency shortens life expectancy, and no reliable survival figures exist [2,3]. Peer support helps, particularly given how new the diagnosis is [4,24].

Thinking about a clinical trial?

Clinical trials test whether a treatment works and whether it is safe. SORD deficiency is a small and very new research field, so studies are few and they come and go. Deciding whether to look into one is personal, and it helps to take it in steps.

1. Understand what the study is asking

It is worth being clear on what a study involves:

• what the researchers are trying to learn, which may be about walking, strength, sorbitol levels or safety rather than a cure
• what is being studied, and what it is compared with, usually a placebo since no approved treatment exists
• how long the study lasts, since nerve conditions change slowly and studies often run a year or more
• what visits and tests are involved, such as timed walking tests, strength measures, blood or urine samples and sometimes scans
• the possible benefits, the known and unknown risks, what happens at the end, and how far you would travel

2. Consider possible medical suitability

Every trial has rules about who can take part, called eligibility criteria. For a SORD deficiency study they might include changes confirmed in both copies of the SORD gene, a raised sorbitol level in blood, being able to walk a set distance without help, an age range, being able to complete timed walking and strength tests reliably, and no other likely explanation for the nerve damage such as diabetes.

trialport’s medifit helps people consider information related to possible medical suitability. It does not diagnose a condition, confirm eligibility or replace formal screening by the study team.

Explore SORD deficiency clinical trials through trialport

3. Consider whether participation fits your life

Medical suitability is only part of the picture. A study can look right on paper and still be hard in practice:

• the time each visit takes, and how many visits there are in total
• travel and distance, which weigh more heavily when walking is difficult
• work, school or caring responsibilities, and time off
• how you would feel if the treatment did not help, or if a study stopped early

trialport’s readifit helps people reflect on their understanding, motivation, time, routines, support, emotions and practical arrangements.

4. Ask questions before deciding

Useful questions to put to a research team:

• Why is this study being carried out, and what is already known about the treatment?
• What exactly would I need to do, and how many visits and tests are involved?
• What are the known risks, and what is still unknown?
• Could I receive a placebo? A placebo is a dummy treatment with no active medicine, used so researchers can compare results fairly. How likely is that here?
• Can I leave after joining, and what happens to my usual care then?
• What happens if the study stops early, and would I be told why?
• Could I keep the treatment afterward, and who would pay for it?
• Are travel costs covered, and who do I contact between visits?

Taking part is voluntary. A person can ask questions, speak with people they trust and choose not to participate.

Search for clinical trials at app.trialport.com.

Current research

Research is moving in three directions: treatment, better testing, and understanding how sorbitol harms nerves.

• Blocking the first step of the pathway. Since the enzyme that turns sorbitol into fructose is missing, one approach is to make less sorbitol in the first place, by blocking the enzyme that makes it, aldose reductase. Medicines that do this, called aldose reductase inhibitors, corrected sorbitol levels and improved movement in laboratory models [1,16]. One of them, govorestat, was tested in a phase 2/3 study called INSPIRE in 56 people. Its main measure, a 10-meter walk and run test at 12 months, showed no significant difference from placebo, though blood sorbitol fell significantly and a patient-reported measure of daily impact improved [17]. In April 2026 the company that had acquired the developer stopped all govorestat studies, including the continuation study and the early access program, while it works out what further evidence regulators require [18]. Govorestat is not approved anywhere for SORD deficiency, and is not currently available in a study [4,18].
• Better and faster testing. Urine sorbitol with xylitol [5], measuring the enzyme’s activity in red blood cells [19], long-read sequencing [10] and the newly described gene inversions [11] all aim at finding people currently missed.
• Understanding the damage. A rat without the SORD enzyme develops a mainly motor neuropathy resembling the human condition, which is helping researchers work out how sorbitol harms nerves [15].

Study status checked: 3 August 2026. Research moves, and what is being studied changes. For current information, search at app.trialport.com.

Support and further information

No organization is dedicated to SORD deficiency alone. Support comes through Charcot-Marie-Tooth organizations, which now cover it explicitly.

The Charcot-Marie-Tooth Association is the most useful starting point: a plain-language page on CMT-SORD, a directory of specialist centers, and clear updates on the govorestat program, including its pause [4,18]. The CMT Research Foundation funds research and summarizes what is in development [25], and the Hereditary Neuropathy Foundation runs a registry for inherited neuropathies and has put the SORD community in front of regulators [24]. Both are in the United States and work internationally, as does the Muscular Dystrophy Association [26]. In the United Kingdom, CMTUK provides membership support and local groups [23].

For general background, the National Institute of Neurological Disorders and Stroke explains Charcot-Marie-Tooth disease [12] and the NHS covers nerve damage generally [13], though neither has a page on SORD deficiency. Coverage is thin elsewhere, and no organization outside these countries could be verified. Where no local group exists, a neuromuscular center is the better starting point.

Questions people often ask

I had genetic testing and it was normal. Could I still have SORD deficiency?
Yes, and this is common. The SORD gene sits beside an almost identical non-working copy that many tests could not tell apart, and tests done before 2020 were not looking for it at all [1,7,10]. Measuring sorbitol is a reasonable question to raise with a neurologist [4,5].

Does it shorten life expectancy?
No published evidence says it does, and no reliable survival figures exist. Follow-up shows slow progression, with most people still walking independently later on [2].

Will my children have it?
It is very unlikely. A child will inherit one changed copy and be a healthy carrier, and would only be affected if the other parent happened to be a carrier too [4].

Is there a treatment?
Not one that slows the condition. Therapy, ankle and foot supports, exercise guidance, surgery in some cases and nerve pain treatment all help [4,20].

Does avoiding sorbitol in food help?
There is no evidence that it does, since the sorbitol that builds up is made inside the body from glucose rather than absorbed from food [1].

Is it connected to diabetes?
The same sugar pathway is involved in the nerve damage caused by diabetes, which is why the discovery interested researchers beyond rare disease [1]. SORD deficiency itself is inherited, and is not caused by diabetes.

Related trialport information

• Search for SORD deficiency clinical trials
• How trialport works
• medifit and readifit explained
• Questions people ask about clinical trials
• More guides to medical conditions
• Related guide: CIDP
• Related guide: myasthenia gravis
• Related guide: type 2 diabetes

Sources

1. Cortese A, Zhu Y, Rebelo AP, et al. Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Nature Genetics. 2020;52(5):473-481. doi:10.1038/s41588-020-0615-4. https://pmc.ncbi.nlm.nih.gov/articles/PMC8353599/ Accessed 3 August 2026.
2. Cortese A, Dohrn MF, Curro R, et al. Genotype and phenotype spectrum of Charcot-Marie-Tooth disease due to mutations in SORD. Brain. 2025;148(10):3737-3747. doi:10.1093/brain/awaf021. https://pmc.ncbi.nlm.nih.gov/articles/PMC12493047/ Accessed 3 August 2026.
3. National Institutes of Health, Genetic Testing Registry. Neuronopathy, distal hereditary motor, autosomal recessive 8: condition summary, synonyms and associated gene, drawn from OMIM entry 618912. https://www.ncbi.nlm.nih.gov/gtr/conditions/C5394466/ Accessed 3 August 2026.
4. Charcot-Marie-Tooth Association (CMTA). CMT-SORD: Sorbitol Dehydrogenase (SORD) Deficiency. https://cmtausa.org/cmt-sord/ Accessed 3 August 2026.
5. Bontrager JE, White AL, Brigatti KW, et al. Urine Sorbitol and Xylitol for the Diagnosis of Sorbitol Dehydrogenase Deficiency-Related Neuropathy. Neurology. 2025;105(11):e214425. doi:10.1212/WNL.0000000000214425. https://pubmed.ncbi.nlm.nih.gov/41223342/ Accessed 3 August 2026.
6. Pons N, Fernandez-Eulate G, Pegat A, et al. SORD-related peripheral neuropathy in a French and Swiss cohort: clinical features, genetic analyses, and sorbitol dosages. European Journal of Neurology. 2023;30(7):2001-2011. doi:10.1111/ene.15793. https://pubmed.ncbi.nlm.nih.gov/36943151/ Accessed 3 August 2026.
7. Lassuthova P, Mazanec R, Stanek D, et al. Biallelic variants in the SORD gene are one of the most common causes of hereditary neuropathy among Czech patients. Scientific Reports. 2021;11:8443. doi:10.1038/s41598-021-86857-0. https://pmc.ncbi.nlm.nih.gov/articles/PMC8055917/ Accessed 3 August 2026.
8. Liu X, He J, Yilihamu M, Duan X, Fan D. Clinical and Genetic Features of Biallelic Mutations in SORD in a Series of Chinese Patients With Charcot-Marie-Tooth and Distal Hereditary Motor Neuropathy. Frontiers in Neurology. 2021;12:733926. doi:10.3389/fneur.2021.733926. https://pmc.ncbi.nlm.nih.gov/articles/PMC8607551/ Accessed 3 August 2026.
9. Arlt A, Akova-Ozturk E, Schirmacher A, et al. SORDD: mutation frequency and phenotype in predominantly axonal Charcot-Marie-Tooth disease of undefined genetic cause. Journal of Neurogenetics. 2024;38(2):35-40. doi:10.1080/01677063.2024.2374898. https://pubmed.ncbi.nlm.nih.gov/38975976/ Accessed 3 August 2026.
10. Grosz BR, Stevanovski I, Negri S, et al. Long read sequencing overcomes challenges in the diagnosis of SORD neuropathy. Journal of the Peripheral Nervous System. 2022;27(2):120-126. doi:10.1111/jns.12485. https://pubmed.ncbi.nlm.nih.gov/35224818/ Accessed 3 August 2026.
11. Quartesan I, Facchini S, Manini A, et al. Gene-Pseudogene Inversions as a Hidden Source of Missing Heritability. medRxiv preprint. 7 October 2025. doi:10.1101/2025.10.01.25336578. https://pmc.ncbi.nlm.nih.gov/articles/PMC12632684/ Accessed 3 August 2026. Not yet peer reviewed.
12. National Institute of Neurological Disorders and Stroke (NINDS). Charcot-Marie-Tooth Disease. https://www.ninds.nih.gov/health-information/disorders/charcot-marie-tooth-disease Accessed 3 August 2026.
13. National Health Service (NHS). Peripheral neuropathy. https://www.nhs.uk/conditions/peripheral-neuropathy/ Accessed 3 August 2026.
14. Furuta Y, Nelson ET, Neumann SM, et al. A medical odyssey of a 72-year-old man with Charcot-Marie-Tooth disease type 2 newly diagnosed with biallelic variants in SORD gene causing sorbitol dehydrogenase deficiency. American Journal of Medical Genetics Part A. 2023;191(12):2873-2877. doi:10.1002/ajmg.a.63383. https://pmc.ncbi.nlm.nih.gov/articles/PMC12340615/ Accessed 3 August 2026.
15. Rebelo AP, Abad C, Dohrn MF, et al. SORD-deficient rats develop a motor-predominant peripheral neuropathy unveiling novel pathophysiological insights. Brain. 2024;147(9):3131-3143. doi:10.1093/brain/awae079. https://pubmed.ncbi.nlm.nih.gov/38538210/ Accessed 3 August 2026.
16. Zhu Y, Lobato AG, Rebelo AP, et al. Sorbitol reduction via govorestat ameliorates synaptic dysfunction and neurodegeneration in sorbitol dehydrogenase deficiency. JCI Insight. 2023;8(10):e164954. doi:10.1172/jci.insight.164954. https://pmc.ncbi.nlm.nih.gov/articles/PMC10322690/ Accessed 3 August 2026.
17. Applied Therapeutics. Applied Therapeutics Presents Full 12-Month Clinical Results and New Topline Data from INSPIRE Phase 2/3 Trial of Govorestat in CMT-SORD. Press release, 18 May 2025. https://www.globenewswire.com/news-release/2025/05/18/3083535/0/en/Applied-Therapeutics-Presents-Full-12-Month-Clinical-Results-and-New-Topline-Data-from-INSPIRE-Phase-2-3-Trial-of-Govorestat-in-CMT-SORD-in-Late-Breaking-Oral-Presentation-at-the-P.html Accessed 3 August 2026.
18. Charcot-Marie-Tooth Association (CMTA). Cycle Pharmaceuticals Stops Clinical Studies of Govorestat. 21 April 2026. https://cmtausa.org/simply-cmt/cycle-pharmaceuticals-stops-clinical-studies-of-govorestat/ Accessed 3 August 2026.
19. Moro N, Francois S, Grondin C, et al. Measurement of Red Blood Cell Sorbitol Dehydrogenase Activity for Fast Screening of SORD-Related Neuropathies. Journal of the Peripheral Nervous System. 2026;31(2):e70122. doi:10.1111/jns.70122. https://pubmed.ncbi.nlm.nih.gov/42021567/ Accessed 3 August 2026.
20. De Grado A, Serio M, Saveri P, Pisciotta C, Pareyson D. Charcot-Marie-Tooth disease: a review of clinical developments and its management, what’s new in 2025? Expert Review of Neurotherapeutics. 2025;25(4):427-442. doi:10.1080/14737175.2025.2470980. https://pubmed.ncbi.nlm.nih.gov/40014417/ Accessed 3 August 2026.
21. Hayes LH, Sadjadi R. Hereditary Neuropathies. Continuum (Minneapolis, Minnesota). 2023;29(5):1514-1537. doi:10.1212/CON.0000000000001339. https://pubmed.ncbi.nlm.nih.gov/37851041/ Accessed 3 August 2026.
22. Dong HL, Li JQ, Liu GL, Yu H, Wu ZY. Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy. npj Genomic Medicine. 2021;6:1. doi:10.1038/s41525-020-00165-6. https://pmc.ncbi.nlm.nih.gov/articles/PMC7782788/ Accessed 3 August 2026.
23. CMTUK. Charcot-Marie-Tooth support in the United Kingdom: what CMT is, membership, local groups, events and the CMT Kids programme. https://www.cmt.org.uk/ Accessed 3 August 2026.
24. Hereditary Neuropathy Foundation. Mission, patient resources, the Global Registry for Inherited Neuropathies, and the 2026 FDA patient listening session for CMT-SORD. https://www.hnf-cure.org/ Accessed 3 August 2026.
25. CMT Research Foundation. Research pipeline, funded projects and news on treatments in development for Charcot-Marie-Tooth disease. https://cmtrf.org/ Accessed 3 August 2026.
26. Muscular Dystrophy Association. Charcot-Marie-Tooth Disease (CMT). https://www.mda.org/disease/charcot-marie-tooth Accessed 3 August 2026.
27. MedGen, National Center for Biotechnology Information. Neuronopathy, distal hereditary motor, autosomal recessive 8 (SORDD; HMNR8), MedGen UID 1714781, Concept ID C5394466, gene location 15q21.1, MONDO:0030055, OMIM 618912. https://www.ncbi.nlm.nih.gov/medgen/1714781 Accessed 3 August 2026.

Review information

Written by: trialport editorial team
Reviewed by: Keith Berelowitz, Founder and CEO, trialport
Reviewed on: 3 August 2026
Next review due: 3 August 2027
References last checked: 3 August 2026