The test measures two sugar alcohols to detect SORD-related neuropathy, which standard genetic tests sometimes miss.
A new urine test that measures sorbitol and xylitol is making diagnosis of SORD-related neuropathy faster and more affordable, potentially expanding access to emerging treatments for this common inherited nerve disorder.
The test, developed through a partnership between the University of Rochester, Mayo Clinic, and the Clinic for Special Children in Pennsylvania, can detect patients that some genetic tests miss at about one-tenth the cost of typical genetic panels, according to researchers. Research describing the test appears in the journal Neurology.
“Having a reliable, low-cost biochemical screen means we can diagnose patients earlier and more cheaply, get them into clinical trials sooner, and begin to learn how the disease changes over time,” says David Herrmann, MBBCh, chief of the University of Rochester neuromuscular division and co-senior author of the study, in a release.
SORD deficiency is believed to be among the most common causes of inherited nerve diseases, but screening for the condition is challenging and it is not included in many current genetic tests. The condition occurs when the SORD gene is not working properly due to mutations in both copies of the gene.
Detecting a Biochemical Signature
The SORD gene makes an enzyme that normally helps convert the sugar alcohol sorbitol into fructose and also helps metabolize xylitol. When SORD activity is lost, both sorbitol and xylitol accumulate, producing a distinct biochemical signature that appears in urine.
“We needed something that clinics could actually use—a test that’s noninvasive, affordable, and sensitive,” says Jordan Bontrager, MS, CGC, genetic counselor at the University of Rochester who collaborated with a team led by Mathew Schultz, PhD, at the Mayo Clinic to validate and expand the assay, in a release. “By validating sorbitol and xylitol together, we now have a screen that catches patient cases, which standard short-read genetic tests sometimes miss.”
SORD deficiency most often presents as an axonal peripheral neuropathy and is commonly diagnosed within the spectrum of Charcot–Marie–Tooth disease or as distal hereditary motor neuropathy. Patients typically develop progressive weakness, especially in the feet and lower legs, and may experience balance or walking difficulties that begin in childhood or early adulthood.
Validation in Amish Communities
The test was validated using samples from Old Order Amish families in Lancaster County, Pennsylvania, where SORD deficiency is believed to be a common cause of progressive motor neuropathy. Clinicians at the Clinic for Special Children identified their initial Amish patient with SORD deficiency through genetic testing, then used cascade screening to reveal the same diagnosis across multiple generations.
Within the Old Order Amish, certain recessive gene variants may be more common due to their shared genetic heritage from a small number of founders in the 18th century, combined with their genetic isolation from the broader population.
“For some families who had long accepted mild, unexplained symptoms as ‘normal,’ this test has brought understanding, access to genetic counseling, and a path to care,” says Bontrager in a release.
Complement to Genetic Testing
Researchers emphasize that the urine test is a powerful complement to genetic testing, not a replacement for it. Larger studies that include people with diabetes and other causes of neuropathy will help define how the test performs in broader clinical settings.
Longer studies are also needed to determine whether urine sorbitol and xylitol track disease progression or respond to treatment, providing information that could make the test useful for both monitoring and diagnosis.
“Turning a gene discovery into a clinic-ready test and then into trials is how we move from bench science to real improvements in patient care,” says Herrmann in a release. “Making testing accurate, affordable, and easy changes who can get diagnosed, and who can get into trials. That can make a real difference for families.”
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