Mitochondrial myopathy without extraocular muscle involvement: a unique clinicopathologic profile

Area of Science:

• Neurology
• Genetics
• Mitochondrial Diseases

Background:

• Mitochondrial myopathy without extraocular muscles involvement (MiMy) is a poorly understood mitochondrial disorder.
• It primarily affects limb and axial muscles, with limited data on its characteristics and prognosis.

Purpose of the Study:

• To comprehensively profile MiMy patients.
• To elucidate the unique clinical, genetic, and pathological features of MiMy.
• To compare MiMy with other mitochondrial diseases like PEO and MELAS.

Main Methods:

• Cross-sectional study of 47 MiMy patients from a national diagnostic center.
• Comparison of clinical, pathological, and genetic data with progressive external ophthalmoplegia (PEO) and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) patients.
• Analysis of muscle biopsies, genetic testing (mtDNA variants and deletions), and clinical assessments including 6-minute walk test (6MWT) and fatigue severity scale (FSS).

Main Results:

• MiMy patients exhibited more severe muscle involvement, lower 6MWT scores, higher FSS, and lower BMI compared to PEO and MELAS.
• Elevated serum CK, lactate, and GDF15 levels were observed in MiMy.
• Typical pathological findings included cytochrome c oxidase strong (COX-s) ragged-red fibers (RRFs), with mtDNA point pathogenic variants being the most common genetic cause.
• Subclinical peripheral neuropathy was present in 31.9% of patients.
• A majority (76.1%) showed stabilization or improvement after treatment.

Conclusions:

• This study provides a detailed profile of MiMy, highlighting its distinct features.
• Findings offer insights for improved diagnosis and management of MiMy.
• The results aim to enhance patient outcomes and quality of life for individuals with MiMy.