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Background <p>Inherited peripheral neuropathies (IPNs) encompass a wide range of disorders affecting the peripheral nervous system, often with complex genetic causes and frequent underdiagnosis. The variants in the superoxide dismutase 1 (<i>SOD1</i>) gene, primarily linked to amyotrophic lateral sclerosis (ALS), have also been associated with peripheral neuropathy. The recent approval of Tofersen, targeting <i>SOD1</i>-related ALS, highlights the importance of precise genetic diagnosis. This study explores the clinical and genetic profiles of <i>SOD1</i>-related IPNs (<i>SOD1</i>-IPN) in a nationwide Japanese IPN cohort.</p> Methods <p>Clinical and genetic data were assessed from 1483 Japanese patients with IPN, with a focus on those harboring <i>SOD1</i> pathogenic variants. The clinical evaluations included age of onset, gender, muscle weakness patterns, sensory disturbances, reflex responses, and electrophysiological findings.</p> Results <p>Seventeen patients with <i>SOD1</i> pathogenic variants were identified, reinforcing <i>SOD1</i>’s role in IPN. The average onset age was 47, with a slight male predominance. Distal muscle weakness was noted in 9 of 13 patients, and asymmetric muscle weakness and atrophy in 10 of 14 cases. Mild sensory disturbances were observed in eight patients, with some showing hyperreflexia and abnormal reflexes. Electrophysiology predominantly indicated a length-dependent, motor-dominant axonal neuropathy.</p> Conclusion <p>This study reveals the clinical variability and likely underdiagnosis of <i>SOD1</i>-IPN, supporting the integration of <i>SOD1</i> screening in IPN genetic testing, especially for patients with asymmetric, length-dependent axonal neuropathy evident in clinical and electrophysiological assessments.</p>

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SOD1-related inherited peripheral neuropathies in a Japanese cohort: genetic variants and clinical insights

  • 期刊论文

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  • 发表日期：

    2025年2月11日

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  • Masahiro Ando,
  • Yujiro Higuchi,
  • Jun-Hui Yuan,
  • Akiko Yoshimura,
  • Chikashi Yano,
  • Takahiro Hobara,
  • Fumikazu Kojima,
  • Yu Hiramatsu,
  • Satoshi Nozuma,
  • Tomonori Nakamura,
  • Yusuke Sakiyama,
  • Akihiro Hashiguchi,
  • Yuji Okamoto,
  • Takeshi Matsushige,
  • Jun Mitsui,
  • Shoji Tsuji,
  • Hiroshi Takashima

摘要

Background

Inherited peripheral neuropathies (IPNs) encompass a wide range of disorders affecting the peripheral nervous system, often with complex genetic causes and frequent underdiagnosis. The variants in the superoxide dismutase 1 (SOD1) gene, primarily linked to amyotrophic lateral sclerosis (ALS), have also been associated with peripheral neuropathy. The recent approval of Tofersen, targeting SOD1-related ALS, highlights the importance of precise genetic diagnosis. This study explores the clinical and genetic profiles of SOD1-related IPNs (SOD1-IPN) in a nationwide Japanese IPN cohort.

Methods

Clinical and genetic data were assessed from 1483 Japanese patients with IPN, with a focus on those harboring SOD1 pathogenic variants. The clinical evaluations included age of onset, gender, muscle weakness patterns, sensory disturbances, reflex responses, and electrophysiological findings.

Results

Seventeen patients with SOD1 pathogenic variants were identified, reinforcing SOD1’s role in IPN. The average onset age was 47, with a slight male predominance. Distal muscle weakness was noted in 9 of 13 patients, and asymmetric muscle weakness and atrophy in 10 of 14 cases. Mild sensory disturbances were observed in eight patients, with some showing hyperreflexia and abnormal reflexes. Electrophysiology predominantly indicated a length-dependent, motor-dominant axonal neuropathy.

Conclusion

This study reveals the clinical variability and likely underdiagnosis of SOD1-IPN, supporting the integration of SOD1 screening in IPN genetic testing, especially for patients with asymmetric, length-dependent axonal neuropathy evident in clinical and electrophysiological assessments.