Diverse myopathological features in the congenital myasthenia syndrome with GFPT1 mutation.

Abstract

INTRODUCTION:

Mutations in the GFPT1 gene are associated with a particular subtype of congenital myasthenia syndrome (CMS) called limb-girdle myasthenia with tubular aggregates. However, not all patients show tubular aggregates in muscle biopsy, suggesting the diversity of myopathology should be further investigated.

METHODS:

In this study, we reported two unrelated patients clinically characterized by easy fatigability, limb-girdle muscle weakness, positive decrements of repetitive stimulation, and response to pyridostigmine. The routine examinations of myopathology were conducted. The causative gene was explored by whole-exome screening. In addition, we summarized all GFPT1-related CMS patients with muscle biopsy in the literature.

RESULTS:

Pathogenic biallelic GFPT1 mutations were identified in the two patients. In patient one, muscle biopsy indicated vacuolar myopathic changes and atypical pathological changes of myofibrillar myopathy characterized by desmin deposits, Z-disc disorganization, and electronic dense granulofilamentous aggregation. In patient two, muscle biopsy showed typical myopathy with tubular aggregates. Among the 51 reported GFPT1-related CMS patients with muscle biopsy, most of them showed tubular aggregates myopathy, while rimmed vacuolar myopathy, autophagic vacuolar myopathy, mitochondria-like myopathy, neurogenic myopathy, and unspecific myopathic changes were also observed in some patients. These extra-synaptic pathological changes might be associated with GFPT1-deficiency hypoglycosylation and altered function of muscle-specific glycoproteins, as well as partly responsible for the permanent muscle weakness and resistance to acetylcholinesterase inhibitor therapy.

CONCLUSIONS:

Most patients with GFPT1-related CMS had tubular aggregates in the muscle biopsy, but some patients could show great diversities of the pathological change. The myopathological findings might be a biomarker to predict the prognosis of the disease.

• Authors: Kaiyan Jiang, Yilei Zheng, Jing Lin, Xiaorong Wu, Yanyan Yu, Min Zhu, Xin Fang, Meihong Zhou, Xiaobing Li, Daojun Hong
• Journal: Brain and behavior (Brain Behav) Vol. 12 Issue 2 Pg. e2469 (02 2022) ISSN: 2162-3279 [Electronic] United States
• PMID: 34978387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

Chemical References

• GFPT1 protein, human
• Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
• Acetylcholinesterase

Topics

• Acetylcholinesterase
• Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) (genetics)
• Humans
• Muscle Weakness
• Muscle, Skeletal (pathology)
• Mutation
• Myasthenic Syndromes, Congenital (diagnosis, genetics)
• Myopathies, Structural, Congenital