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Exploratory analysis of lower limb muscle MRI in a case series of patients with SORD neuropathy
  1. Luke Francis O'Donnell1,
  2. Andrea Cortese1,2,
  3. Alexander M Rossor1,
  4. Matilde Laura1,
  5. Julian Blake1,3,
  6. Mariola Skorupinska1,
  7. Michael P Lunn1,
  8. John S Thornton1,4,
  9. Riccardo Currò1,2,
  10. Jasper M Morrow1,
  11. Mary M Reilly1
  1. 1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK
  2. 2Department of Brain and Behavioural Sciences, University of Pavia, Pavia PV, Italy
  3. 3Department of Clinical Neurophysiology, Norfolk and Norwich University Hospital, Norwich, UK
  4. 4Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK
  1. Correspondence to Professor Mary M Reilly, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, WC1N 3BG London, UK; m.reilly{at}ucl.ac.uk

http://dx.doi.org/10.1136/jnnp-2022-329432

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    Introduction

    Recently biallelic mutations in the sorbitol dehydrogenase (SORD) gene were reported as representing a frequency of up to around 10% in undiagnosed cases of Charcot-Marie-Tooth disease 2 (CMT2) and distal hereditary motor neuropathy (dHMN).1 SORD is an enzyme in the two-step polyol pathway for the conversion of glucose to fructose with deficiencies in SORD shifting the balance towards increased sorbitol levels.1 Cortese et al1 have demonstrated in preclinical studies that using aldose reductase inhibitors led to a reduction of sorbitol levels in patient-derived fibroblasts. SORD neuropathy may therefore be a target for therapeutic trials in the near future.

    Responsive outcome measures are needed for clinical trials, and the rationale for using MRI of lower limbs over other outcome measures in CMT is the ability to quantify fat fraction in muscle over time and its correlation with clinical parameters.2 We have previously shown quantitative calf MRI intramuscular fat fraction to have high responsiveness in two different inherited neuropathies, CMT1A and hereditary sensory neuropathy type 1 using the Medical Research Council (MRC) Centre Muscle MRI Protocol.2 3

    In this exploratory study, we report the lower limb muscle MRI findings in a series of patients with SORD neuropathy, examining the distribution of fat accumulation, atrophy and oedema and report potential clinical correlations.

    Methods

    Using our genetic database from the UCL Queen Square Institute of Neurology, London, UK, we identified patients with SORD-associated neuropathy who had confirmed biallelic pathogenic variants in the SORD gene.1 We retrospectively analysed all patients who had an MRI scan of calf and thigh muscles performed as part of standard clinical care comprising standard axial T1-weighted and short-tau inversion recovery (STIR) sequences on 3T MRI. Clinical data were acquired retrospectively from patient records as close as possible to the time …

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    Footnotes

    • JMM and MMR contributed equally.

    • Contributors LFO'D collected data, performed the primary analysis and wrote the manuscript. JMM and MMR contributed equally to this paper. JMM was responsible for the paper concept and design, data collection, primary analysis, writing the manuscript and edits. MMR was responsible for the paper concept and design, data collection, primary analysis writing the manuscript and edits. AC, AMR, ML, JB, MS, MPL, JST and RC were responsible for data interpretation and edits.

    • Funding LFO'D is funded by the NIH grant Accelerate Clinical Trials in CMT (1UOINS109403-01). AC would like to thank the Medical Research Council (MR/T001712/1), the Fondazione CARIPLO (2019-1836), the Inherited Neuropathy Consortium (INC) and Fondazione Regionale per la Ricerca Biomedica for grant support. MMR acknowledges support from the National Institutes of Neurological Diseases and Stroke and office of Rare Diseases (U54NS065712 and 1UOINS109403-01 and R21TROO3034), Muscular Dystrophy Association (MDA510281), the Medical Research Council (MRC MR/S005021/1) and the Charcot Marie Tooth Association (CMTA) for their support. RC was supported by the European Academy of Neurology Research Fellowship 2021. This research was also supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.