Charcot-Marie-Tooth disease (CMT) is named after the three doctors who first described it in 1886: Jean-Martin Charcot (shar-coh), Pierre Marie, and Howard Henry Tooth. Today, CMT refers to any peripheral neuropathy with a genetic cause, whether or not the specific genetic mutation is known.
CMT-SORD, also known as Sorbitol Dehydrogenase (SORD) Deficiency, is a recently identified subtype of CMT. Discovered in 2020 through CMTA-supported research, CMT-SORD is linked to mutations in the SORD gene and highlights the critical role of genetic research in unlocking new understandings of CMT.
What is CMT-SORD?
CMT-SORD is caused by mutations in the SORD gene, which lead to the buildup of a type of sugar called sorbitol. CMT-SORD is the only CMT subtype where this happens, making it a truly unique subtype. As sorbitol accumulates, it becomes toxic to peripheral nerves, resulting in symptoms such as muscle weakness and sensory loss. CMT-SORD is an axonal form of CMT, meaning it primarily affects the part of the nerve responsible for transmitting signals.
How is CMT-SORD Related to CMT?
CMT-SORD is classified as an axonal neuropathy. Many with CMT-SORD are first clinically diagnosed with CMT2 or distal hereditary motor neuropathy (dHMN, also called HMN – hereditary motor neuropathy). dHMN/HMN is also an axonal classification for CMT subtypes.
How is CMT-SORD Diagnosed?
Diagnosing CMT-SORD involves the following steps:
- Clinical evaluation: A doctor assesses muscle weakness, impaired mobility, and other CMT-SORD symptoms.
- Sorbitol measurement: Highly elevated levels of sorbitol in blood or urine are indicative of CMT-SORD.
- Genetic testing: Genetic testing for CMT-SORD can identify mutations in the SORD gene.
Can You Have CMT-SORD Without a Family History?
Yes. CMT-SORD is inherited in an autosomal recessive manner, meaning a person must inherit two copies of the mutated SORD gene—one from each parent—to develop the condition. People with CMT-SORD are often the first in their family to have CMT, as is typical with autosomal recessive types of CMT. It’s also possible to have CMT-SORD without inheriting any SORD gene mutations (called a “de novo” case).
If you have CMT-SORD, your children are not expected to have CMT. As is the case with all autosomal recessive types of CMT, your children, however, will inherit one copy of the SORD gene mutation, and will be “carriers,” but will not have CMT. To learn more about autosomal recessive inheritance, visit our CMT Inheritance page.
How is CMT-SORD Treated?
Treating CMT-SORD focuses on individualized symptom management. While there is no FDA-approved treatment yet, many symptoms can be effectively managed. Common approaches include:
- Physical and occupational therapy
- Foot and ankle orthoses (AFOs)
- Staying active with appropriate guidance
- Surgery to correct foot deformities when needed
Receiving care at a CMTA Center of Excellence is one of the best ways to manage CMT-SORD. CMTA Centers of Excellence are staffed by expert CMT physicians, clinicians, and researchers who provide comprehensive, CMT-focused, patient-centered care.
Ongoing CMT-SORD Research
CMT-SORD research is moving quickly. CMTA-STAR Alliance Partner Applied Therapeutics conducted the Phase III INSPIRE trial for govorestat (AT-007), a potential treatment that may help lower harmful sorbitol levels and slow disease progression. While not FDA-approved, these clinical efforts reflect significant progress toward therapeutic options for people with CMT-SORD.
CMTA’s Role in Advancing CMT-SORD Research
The discovery of the SORD gene mutation was made possible through CMTA-funded research. CMTA’s Strategy to Accelerate Research (CMTA-STAR) has supported every step from discovery to clinical trial readiness. Working closely with research partners like the Inherited Neuropathy Consortium (INC), CMTA-STAR helped develop critical clinical trial tools such as:
- The CMT Functional Outcomes Measure (CMT-FOM), which tracks changes in function
- The CMT Health Index (CMT-HI), which captures the patient-reported impact of symptoms
CMTA’s Patients as Partners in Research program also made rapid trial recruitment possible by connecting the CMT community with researchers and industry leaders.
Through these combined efforts, CMT-SORD advanced from genetic discovery to a Phase III clinical trial within two years, a significant step forward in CMT research.
Sponsored Sorbitol Testing Now Available
Applied Therapeutics has launched a sponsored urine sorbitol testing program to help healthcare providers identify patients with suspected CMT-SORD. This urine test, called a polyol urinalysis and available from Mayo Clinic (test code SORD), checks specific sugar levels, including sorbitol. In CMT-SORD, sorbitol levels are very high in urine and can confirm a suspected CMT-SORD diagnosis.
The company reports that this sponsored testing is available at no cost to patients and caregivers who qualify, removing potential barriers to diagnosis, care management, and future treatment. A licensed healthcare provider with a registered National Provider Identifier (NPI) number can order the test here: https://sorbitolassayrequest.com/. Mayo clinic will send the test kit to the provider after it’s been ordered.
Register With Patients as Partners in Research Today
Not yet registered with CMTA’s Patients as Partners in Research? Sign up today to be among the first to learn about new CMT research opportunities for which you may be eligible. Registration also ensures you receive updates on the latest research news and developments.
Registration is free, and everyone with CMT is invited to participate.
Find a CMTA Center of Excellence
CMTA Centers of Excellence offer expert care for individuals with CMT, including those with CMT-SORD. Visit the CMTA Center of Excellence directory to find a location near you.
