Peripheral nerve pathology in VAPB-associated amyotrophic lateral sclerosis with dysautonomia in a Chinese family

Clin Neuropathol. 2020 Nov/Dec;39(6):282-287. doi: 10.5414/NP301281.

Abstract

Mutations of the vesicle-associated membrane protein-associated protein B (VAPB) gene have been identified in familial amyotrophic lateral sclerosis (ALS) with dysautonomia. Here we report the peripheral nerve pathology in ALS with dysautonomia caused by the p.Pro56Ser mutation of the VAPB gene in a Chinese family. The clinical features in all patients were camptocormia, fasciculation, and weakness in all limbs. Two patients developed symptoms of dysautonomia, including abdominal bloating, orthostatic hypotension, constipation, frequent urination, decreased sweating, and burning feet. Electromyography showed widespread neuropathic damage. The sympathetic skin response was absent in the soles of the feet. Sural nerve biopsy revealed loss of nerve fibers, especially unmyelinated fibers. Electron microscopy revealed regional loss of unmyelinated fibers with numerous collagen pockets. This report indicates that VAPB-associated ALS may be accompanied by multifocal autonomic nerve damage.

Publication types

  • Case Reports

MeSH terms

  • Amyotrophic Lateral Sclerosis / complications
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / pathology
  • Asian People
  • Humans
  • Male
  • Middle Aged
  • Muscular Atrophy, Spinal / metabolism
  • Muscular Atrophy, Spinal / pathology
  • Mutation / genetics
  • Pedigree
  • Peripheral Nerves / metabolism*
  • Peripheral Nerves / pathology
  • Primary Dysautonomias / complications
  • Primary Dysautonomias / metabolism*
  • Spinal Curvatures / metabolism
  • Spinal Curvatures / pathology
  • Vesicular Transport Proteins / metabolism*

Substances

  • VAPB protein, human
  • Vesicular Transport Proteins

Supplementary concepts

  • Camptocormia