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What is SORD?
Sorbitol dehydrogenase (SORD) Deficiency, or CMT-SORD, is a recently discovered type of Charcot-Marie-Tooth disease (CMT).
Is SORD related to CMT?
Many people living with SORD Deficiency currently have a diagnosis of Charcot-Marie-Tooth disease Type 2 (CMT2) or distal hereditary motor neuropathy (dHMN). SORD Deficiency is one of the most common recessive causes of hereditary neuropathy.
The recent discovery that disease symptoms in CMT2 and dHMN can be caused by genetic mutations in the SORD enzyme now gives people living with SORD Deficiency and their physicians greater understanding of their specific disease. It also provides the opportunity to participate in a clinical trial of an investigational new treatment targeting the underlying cause of SORD Deficiency.
If you suspect that you may have SORD Deficiency, we encourage you to fill out our submission form for Patients as Partners in Research to volunteer for SORD clinical trials.
What happens in the body of someone living with SORD Deficiency?
Glucose is a simple sugar that the body converts into fructose for energy. One of the ways the body breaks down glucose is through a two-step metabolic pathway.
In this metabolic pathway, two enzymes work to process glucose and then sorbitol.
In the first step, the enzyme Aldose Reductase metabolizes glucose into sorbitol
In the second step, the enzyme Sorbitol Dehydrogenase (SORD) converts sorbitol into fructose
Symptoms in those with SORD Deficiency CMT are caused by toxic high levels of sorbitol in the body.
The human body metabolizes glucose to sorbitol, which is then further broken down to fructose, and then used for energy. In SORD Deficiency, the body is unable to metabolize sorbitol to fructose, and sorbitol accumulates. Accumulation of sorbitol is toxic to cells and tissues, resulting in significant weakness and disability. Individuals with SORD Deficiency have >100 times the sorbitol concentration in their blood compared with unaffected individuals.
What causes SORD Deficiency?
The newly discovered type of CMT is caused by a mutated SORD (sorbitol dehydrogenase) gene that raises sorbitol levels so high they cause axonal damage to peripheral nerves.
What are the symptoms of SORD?
People with SORD deficiency experience progressive neuropathy. Excess toxic sorbitol can lead to various symptoms, which can worsen over time, and may include:
Difficulty walking, which can range from mild (stumbling) to severe (need for a walker or wheelchair, and in some cases near-paralysis)
Foot deformities, with potential need and use of orthotics
Muscle weakness in the arms and legs
98% will have weakness in their legs
59% will have weakness in their arms
Twitching or tremors
Sensory impairment
Neuropathic pain
When do symptoms of SORD start?
Symptoms of SORD Deficiency often start around age 17, but can happen at any time between the ages of 9 and 25.
How is SORD Deficiency diagnosed?
SORD Deficiency is clinically diagnosed in patients when there is presence of a slowly progressive neuropathy, often accompanied by foot deformities. SORD Deficiency can also be diagnosed through genetic testing and motor nerve conduction velocity (MNCV) testing.
What are the treatment options for SORD?
It’s true that CMT does not currently have any FDA-approved treatments, however the many presentations of CMT are treatable and manageable, and this is true for SORD Deficiency CMT also.
SORD Deficiency causes many of the symptoms common with other CMT subtypes.
Traditional management focuses solely on monitoring and addressing symptoms, such as providing pain medicine and getting orthotics or surgery to address foot deformities.
How many people have SORD Deficiency CMT?
SORD Deficiency is the most common autosomal recessive CMT subtype, affecting an estimated 3,300 individuals in the United States alone.
Since CMT-SORD is autosomal recessive in inheritance, most who have it are unlikely to have a prior family history of CMT.
What research is being done around SORD?
Scientists are researching ways to help with the treatment of SORD deficiency. For example, it is hypothesized that blocking the enzyme Aldose Reductase may help normalize sorbitol levels and manage the symptoms of the disease. For these reasons, researchers believe CMT-SORD might be the first treatable CMT type.
If you are interested in being screened for this new subtype and want to be contacted in the near future, please fill out a Patients as Partners in Research profile. The criteria for screening are: 1) you have received a diagnosis of CMT, but genetic testing did not reveal with certainty the responsible gene; 2) your parents never had CMT symptoms.
