Challenges in Diagnosing Rhabdomyolysis: Lesson Learned from a Patient with a Mitochondrial DNA Mutation
Emanuele Barca1, Nuri Jacoby4, Ali Naini2, Michael Miller2, Kurenai Tanji2, Saba Tadesse3, Michio Hirano1
1Columbia University Medical Center, 2Department of Pathology and Cell Biology, 3Department of Neurology, Columbia University Medical Center, 4Department of Neurology, SUNY Downstate Health Sciences University, Maimonides Medical Center
Objective:
To describe the clinical, neuropathological, and genetic features of a patient with recurrent rhabdomyolysis due to a variant in mitochondrial DNA (mtDNA)
Background:
Rhabdomyolysis is characterized by acute, massive muscle fibers breakdown; affected individuals experience muscle pain, fatigue, elevation of creatine kinase (CK), and pigmenturia, which can lead to acute renal failure. Among non-traumatic causes, energy failure is one of the prevalent etiologies. Despite novel high-throughput genetic testing, patients often experience a long, expensive diagnostic odyssey
Design/Methods:
NA
Results:

A 41-year-old woman presented with recurrent rhabdomyolysis over one year. She noticed non-specific muscle pain dating 12 years before the presentation. In 2022, she was diagnosed with coronary artery disease requiring intervention. Following the procedure, she developed generalized malaise and severe muscle pain, accompanied by elevated creatinine and CK to 5,000 U/L; she was diagnosed with statin-induced nephropathy and myopathy. Despite statin discontinuation, she continued to have muscle pain triggered by mild physical activity. In September 2023, she experienced a severe episode of myalgias and weakness; her CK was 15,000 U/L. Clinical Whole-Exome sequencing was negative. mtDNA sequencing from buccal swab identified an 11% mutation load in MT-TF (m.610T>C) and 6% heteroplasmic variant in MT-COIII (m.9544G>A). Muscle biopsy showed 25-35% COX-negative fibers with no ragged-red fibers, muscle mtDNA analysis revealed 8.2% heteroplasmy of the MT-TF variant but 55% mutation load of the MT-COIII variant, supporting the diagnosis of mitochondrial myopathy

Conclusions:

This report of a metabolic myopathy due to a novel MT-COIII variant exemplifies several obstacles we face in diagnosing patients with metabolic myopathies. The initial presentation is often nonspecific, delaying correct referral. Also, the current commonly used genetic panels for myopathies do not include mtDNA analysis, thus underestimating these conditions. Furthermore, mtDNA disorders are highly tissue-specific and may require target tissue genetic and biochemical analyses of the affected tissues to confirm the diagnosis

10.1212/WNL.0000000000211133
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.