Urine Test Detects Inherited Neuropathy Missed by Genetic Screening

Symptoms such as progressive leg weakness, balance problems, and childhood-onset motor difficulties are easily mistaken for other neuropathies. Standard testing demands expensive sequencing panels that struggle to distinguish the SORD gene from its nearly identical pseudogene, delaying answers for families. Researchers have now developed a simple biochemical assay that detects the condition using two sugar alcohols in urine.

The assay was developed by researchers at the University of Rochester (Rochester, NY, USA) and collaborators by expanding an earlier sorbitol test to simultaneously measure xylitol. The test reflects the biochemical signature caused by loss of SORD enzyme activity, which leads to accumulation of both sugar alcohols when the gene is mutated. This approach emerged from years of CMT research, including early patient identification, whole-genome sequencing, and cell-based studies that first clarified the role of SORD in hereditary neuropathy.

The study, published in Neurology, showed that the urine test reliably detects SORD deficiency, even in individuals missed by short-read sequencing. Clinical teams used urine samples from multiple families, including Old Order Amish communities, and demonstrated that the sorbitol–xylitol signature clearly distinguished affected individuals from unaffected relatives. The assay is noninvasive, requires no blood draw, and costs roughly one-tenth as much as standard genetic panels.

These findings show why early biochemical screening matters. Faster detection reduces diagnostic odysseys, allows earlier genetic counseling, and identifies patients eligible for emerging therapies designed to reduce sorbitol buildup. The test also avoids pitfalls caused by the SORD pseudogene and may prove especially valuable for children who require gentler sampling methods. As gene-targeted treatments advance, early identification will help clinicians monitor disease trajectories and evaluate new therapies more effectively.

Researchers are now expanding validation to broader patient groups, including individuals with diabetes or other neuropathies that could influence sorbitol levels. Longer-term studies will determine whether urine biomarkers correlate with disease progression or treatment response, which could turn the test into a dual diagnostic and monitoring tool. Its developers emphasize that biochemical testing complements, rather than replaces, genetic sequencing, helping confirm or clarify results when mutations are hard to interpret.

“We needed something that clinics could actually use—a test that’s noninvasive, affordable, and sensitive,” said University of Rochester genetic counselor Jordan Bontrager, MS, CGC. “By validating sorbitol and xylitol together, we now have a screen that catches patient cases, which standard short-read genetic tests sometimes miss, and it’s about one-tenth the cost of typical genetic panels.”

“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,” said David Herrmann, MBBCh, co-senior author of the research.

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