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Background: Charcot-Marie-Tooth disease (CMT), a slowly advancing hereditary nerve disorder, presents a significant challenge in the medical field. Effective drugs for treatment are lacking, and we struggle to find sensitive markers to track the disease's severity and progression. In this study, our objective was to investigate the levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), fibroblast growth factor 21 (FGF-21) and growth differentiation factor 15 (GDF-15) in individuals with CMT and to compare them to a control group. Our primary goal is to determine whether these biomarker levels are related to the severity of the disease., Methods: Initially, 44 patients with CMT and 44 controls participated in this study. CMT diagnosis was approved by genetic testing. Disease severity was assessed through clinical evaluations using the CMT Neuropathy Score version 2 (CMTNSv2). NfL and GFAP concentrations were measured using Single molecule array, while FGF-21 and GDF-15 concentrations were measured by enzyme-linked immunosorbent assays., Results: In the group of patients with CMT, the concentrations of GDF15, FGF21, NfL, and GFAP were significantly higher than in the control group ( p  < 0.05). NfL and GFAP levels were correlated with the CMTNSv2 score (rs = 0.46, p  = 0.002; rs = 0.31, p  = 0.04)., Conclusion: Our study has provided confirmation that plasma concentrations of NfL, GFAP, GDF15, and FGF21 are significantly elevated in patients with CMT compared to controls. Furthermore, NfL and GFAP levels were correlated with the clinical severity of CMT. These findings suggest that NfL and GFAP can be reliable disease indicators in future research., Competing Interests: HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Pretkalnina, Kenina, Gailite, Rots, Blennow, Zetterberg and Kenina.)

HINT1 is an ubiquitous homodimeric purine phosphoramidase belonging to the histidine-triad superfamily. In neurons, HINT1 stabilizes the interaction of different receptors and regulates the effects of their signaling disturbances. Changes in HINT1 gene are associated with autosomal recessive axonal neuropathy with neuromyotonia. Aim of the study was detailed description of patients' phenotype with HINT1 homozygous NM&#95;005340.7: c.110G>C (p.Arg37Pro) variant. Seven homozygous and three compound heterozygous patients were recruited and evaluated using standardized tests for CMT patients, in four patients' nerve ultrasonography was performed. The median age of symptom onset was 10 years (range 1-20), with initial complaints being distal lower limb weakness with gait impairment, combined with muscle stiffness, more pronounced in the hands than in the legs and worsened by cold. Arm muscles became involved later, presenting with distal weakness and hypotrophy. Neuromyotonia was present in all reported patients and is thus a diagnostic hallmark. Electrophysiological studies demonstrated axonal polyneuropathy. Impaired mental performance was observed in six out of ten cases. In all patients with HINT1 neuropathy, ultrasound examination showed significantly reduced muscle volume as well as spontaneous fasciculations and fibrillations. The nerve cross-sectional areas of the median and ulnar nerves were closer to the lower limits of the normal values. None of the investigated nerves had structural changes. Our findings broaden the phenotype of HINT1 -neuropathy and have implications for diagnostics and ultrasonographic evaluation of HINT1 -neuropathy patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rozevska, Rots, Gailite, Linde, Mironovs, Timcenko, Linovs, Locmele, Micule, Lace and Kenina.)

Background: Spinal and bulbar muscular atrophy (SBMA) or Kennedy disease [OMIM: 313200] is a rare X-linked neuromuscular disease. Patients commonly present with muscle cramps, tremors, leg weakness, dysarthria and dysphagia. Methods: We deeply phenotyped and evaluated the possible extent of affected systems in all patients with SBMA in Latvia ( n = 5). In addition, neurophysiological studies and blood analyses were used to perform a molecular diagnosis and evaluate biochemical values. We analyzed neurofilament light (NfL) as a possible biomarker. Results: Neurological examination revealed typical SBMA clinical manifestations; all patients had small or large nerve fiber neuropathy. Three of five patients had increased neurofilament light levels. Conclusion: The study confirms the systemic involvement in patients suffering from SBMA. Increased NfL concentration was associated with either peripheral neuropathy or decreased body mass index. The complex phenotype of the disease should be kept in mind, as it could help to diagnose patients with SBMA., Competing Interests: VP was employed by BIOCON Medical Laboratory, LCC BIOCON. HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure, and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Millere, Rots, Glazere, Taurina, Kurjane, Priedite, Gailite, Blennow, Zetterberg and Kenina.)