X-linked myopathy with excessive autophagy: a failure of self-eating

Area of Science:

• Neurology
• Genetics
• Cell Biology

Background:

• Autophagic vacuolar myopathies (AVMs) are characterized by excessive autophagosome accumulation in muscle tissue.
• X-linked myopathy with excessive autophagy (XMEA) is a primary AVM, typically presenting with proximal muscle weakness and elevated creatine kinase.
• Other conditions, including Pompe disease, Danon disease, and chloroquine toxicity, can also exhibit autophagic myopathy features.

Purpose of the Study:

• This review focuses on X-linked myopathy with excessive autophagy (XMEA).
• It aims to discuss the clinical presentation, pathology, genetic basis, and potential therapeutic strategies for XMEA.

Main Methods:

• Review of existing literature on XMEA and related autophagic myopathies.
• Analysis of histopathological findings in skeletal muscle biopsies.
• Examination of genetic mutations in the VMA21 gene.

Main Results:

• XMEA presents with progressive proximal weakness, elevated creatine kinase, and characteristic muscle pathology including autophagic vacuoles and complement deposition.
• Mutations in the VMA21 gene impair lysosomal hydrolase activity by affecting V-ATPase assembly, leading to lysosomal dysfunction.
• This dysfunction results in secondary autophagy induction and autophagolysosome accumulation.

Conclusions:

• XMEA is a lysosomal disorder caused by VMA21 mutations affecting V-ATPase function.
• Understanding the pathogenesis of XMEA is crucial for developing targeted therapies.
• Further research into lysosomal disorders of muscle and therapeutic interventions for XMEA is warranted.