Objective: To describe the first case of concomitant spastic paraplegia type 7 (SPG7) and myoclonic epilepsy with ragged red fibers (MERRF) in a patient with progressive gait impairment, ataxia, and myoclonus.

Background: The differential diagnosis of gait imbalance and parkinsonism is broad, and genetic testing has become an essential tool to provide accurate diagnoses and counseling for family planning. SPG7 mutations can cause hereditary spastic paraplegia, and mitochondrial dysfunction has been documented due to deficient expression of paraplegin¹. Seizures and myoclonus usually characterize MERRF but can also manifest with ataxia, optic atrophy, myopathy, and neurocognitive changes. This is to our knowledge the first case of overlapping SPG7 and MERRF syndromes.

Method: Case report.

Results: A 43-year-old man with a family history of MERRF presented for evaluation of progressive gait instability, multiple falls, bradykinesia, ataxia, and dysphonia for the past ten years. He also complained of muscle cramps and twitching. On exam had proximal weakness in the lower extremities, left-sided spasticity with hyperreflexia, myoclonus, left-sided dysmetria, and a wide-based gait. A brain MRI was obtained and showed significant atrophy of the vermis and cerebellar hemispheres (Figure 1). The patient was initially diagnosed with MSA-C. EMG/NCS was initially normal but was repeated and showed sensory polyneuropathy. The patient complained of visual problems and was diagnosed with fundus flavimaculatus. Additional work-up showed elevated plasma alanine and urine lactate and pyruvate. Genetic testing was done and showed two pathogenic variants in the SPG7 gene and a pathogenic variant in the mitochondrial DNA (mtDNA), m.8344.A>G at 67% heteroplasmy.

Conclusion: Mitochondrial dysfunction can present with impairments in multiple systems and might be secondary to single or multiple mutations in the somatic or mtDNA. This is the first case of overlapping SPG7 and MERRF syndromes. Differential diagnosis in patients with ataxia, parkinsonism, or gait disorders should include mitochondrial diseases².

Figure 1

References: 1. Wali G, Kumar KR, Liyanage E, Davis RL, Mackay-Sim A, Sue CM. Mitochondrial Function in Hereditary Spastic Paraplegia: Deficits in SPG7 but Not SPAST Patient-Derived Stem Cells. Front Neurosci. 2020 Aug 20;14:820. doi: 10.3389/fnins.2020.00820. PMID: 32973427; PMCID: PMC7469654.

2. Pedroso JL, de Rezende Pinto WBV, Barsottini OGP, Oliveira ASB. Should we investigate mitochondrial disorders in progressive adult-onset undetermined ataxias? Cerebellum Ataxias. 2020 Aug 24;7:13. doi: 10.1186/s40673-020-00122-0. PMID: 32922825; PMCID: PMC7444269.

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