Journal article
Urine Sorbitol and Xylitol for the Diagnosis of Sorbitol Dehydrogenase Deficiency-Related Neuropathy
Neurology, Vol.105(11), e214425
12/09/2025
DOI: 10.1212/WNL.0000000000214425
PMID: 41223342
Abstract
Sorbitol dehydrogenase (SORD) deficiency, due to biallelic loss-of-function variants in the
gene, is a recently recognized cause of autosomal recessive hereditary neuropathy. Specific diagnosis is difficult on clinical grounds alone, and molecular genetic testing of
is complicated by the presence of a pseudogene. Biochemical testing of serum sorbitol is suggested as a potential biomarker. We report a novel urine biochemical profile of elevated excretion of sorbitol and a second polyol, xylitol, to aid in the identification of individuals with SORD-related neuropathy.
Patients with confirmed or suspected SORD-related neuropathy were recruited by clinicians from 7 academic medical centers and 1 nonprofit specialty care center. Urine was analyzed by a clinically validated, gas chromatography-mass spectrometry assay to measure sorbitol and xylitol excretion. Over 700 reference samples were evaluated from residual clinical samples. Clinical and molecular findings were gathered using a standardized questionnaire.
Nineteen individuals with a clinical and genetic diagnosis of SORD-related neuropathy (median age 31 years, 47% female) and 715 reference samples were used to determine the initial performance of this index urine test. The median sorbitol excretion in affected individuals was 638 mmol/mol creatinine (1st percentile of disease range = 456; reference median = 7, reference 99th percentile = 198). The median xylitol excretion was 1,577 mmol/mol creatinine (1st percentile of disease range = 1,242; reference median = 7, reference 99th percentile = 102). In this patient cohort, the combination of sorbitol and xylitol yielded 100% sensitivity and specificity for SORD-related neuropathy. Four additional individuals who had clinical phenotypes compatible with SORD-related neuropathy had abnormal urine sorbitol/xylitol profile, 2 with genotypes involving a variant of unknown significance in
and 2 with a single heterozygous pathogenic
variant detected, whereas normal urine sorbitol/xylitol levels were observed in 11 asymptomatic, heterozygous carriers.
These data demonstrate the clinical utility of urine sorbitol and xylitol analysis in the screening and diagnosis of SORD deficiency-related neuropathy. In addition, this is the first description of elevated xylitol in SORD deficiency as a clinically informative biomarker, which may increase the specificity of biochemical testing.
Details
- Title: Subtitle
- Urine Sorbitol and Xylitol for the Diagnosis of Sorbitol Dehydrogenase Deficiency-Related Neuropathy
- Creators
- Jordan Elliott Bontrager - University of Rochester Medical CenterAmy L White - Mayo Clinic in ArizonaKarlla W Brigatti - Clinic for Special ChildrenWilliam Laxen - Mayo Clinic in ArizonaPerry R Loken - Mayo Clinic in ArizonaTiffany Grider - University of IowaDevin Oglesbee - Mayo Clinic in ArizonaDimitar K Gavrilov - Mayo Clinic in ArizonaSilvia Tortorelli - Mayo Clinic in ArizonaPatricia L Hall - Mayo Clinic in ArizonaDietrich Matern - Mayo Clinic in ArizonaEmily Lauer - Mayo Clinic in ArizonaAngela Pickart - Mayo Clinic in ArizonaKyle Salsbery - Mayo Clinic in ArizonaZhiyv Niu - Mayo Clinic in ArizonaChristy Smith - Johns Hopkins UniversityAmy Albright - Clinic for Special ChildrenBipasha Mukherjee-Clavin - Johns Hopkins MedicinePooja Parmar - Duke UniversityJustin Mhoon - Duke UniversityRami Massie - McGill UniversityCamille Pilon-CadieuxAmelie GauthierJosef Alawneh - Sheikh Shakhbout Medical CityCam-Tu Émilie NguyenMichael E Shy - University of Iowa Health CareAlanna E Koehler - Clinic for Special ChildrenVincent J Carson - Clinic for Special ChildrenDavid N Herrmann - University of Rochester Medical CenterMatthew J Schultz - Mayo Clinic in Arizona
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.105(11), e214425
- DOI
- 10.1212/WNL.0000000000214425
- PMID
- 41223342
- NLM abbreviation
- Neurology
- ISSN
- 1526-632X
- eISSN
- 1526-632X
- Language
- English
- Date published
- 12/09/2025
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9985027460502771
Metrics
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