Objective: To report a case of juvenile-onset parkinsonism associated with bilateral striatal necrosis and a pathogenic MT-ND3 mitochondrial DNA variant, emphasizing an atypical mitochondrial phenotype relevant to movement disorder practice.

Background: Mitochondrial parkinsonism is an uncommon cause of early-onset parkinsonian syndromes. While most reported cases involve nuclear DNA mutations, mitochondrial DNA variants are rare and usually associated with multisystem or neurodevelopmental phenotypes. Bilateral striatal necrosis on neuroimaging suggests a metabolic or mitochondrial etiology rather than primary neurodegenerative Parkinson’s disease.

Method: A 19-year-old right-handed female with a history of progressive movement disorder since childhood was evaluated. The clinical phenotype was characterized by generalized rigidity, bradykinesia, gait impairment, and later bulbar involvement. Diagnostic workup included neurological examination, metabolic and laboratory studies, brain CT and MRI, cardiac and neuro-ophthalmologic assessment, and whole exome sequencing with mitochondrial DNA analysis.

Results: Neuroimaging revealed chronic bilateral parenchymal sequelae involving the caudate nuclei and putamina, consistent with bilateral striatal necrosis. Genetic testing identified a heteroplasmic pathogenic variant in the mitochondrial gene MT-ND3 (m.10197G>A; p.Ala47Thr), with a heteroplasmy level of 76%, confirming a maternally inherited mitochondrial disorder. This variant affects a subunit of mitochondrial respiratory chain complex I and has been associated with a spectrum of mitochondrial encephalopathies. Clinically, the patient exhibited a levodopa-responsive parkinsonian syndrome, with improvement in rigidity, bradykinesia, and tremor, although dose escalation was limited by orthostatic hypotension and paradoxical rigidity. No significant multisystem involvement was identified.

Conclusion: This case expands the phenotypic spectrum of MT-ND3–related mitochondrial disease by demonstrating that juvenile-onset parkinsonism with bilateral striatal necrosis may represent a predominant clinical presentation. Recognition of characteristic neuroimaging findings and targeted mitochondrial genetic testing is essential for accurate diagnosis and management of early-onset parkinsonism in clinical practice.

Non-contrast brain CT.

Brain MRI with gadolinium.

References: Lopriore P, Palermo G, Meli A, Bellini G, Benevento E, Montano V, et al. Mitochondrial parkinsonism: A practical guide to genes and clinical diagnosis. Movement Disorders Clinical Practice. 2024;11(8):948–965. doi:10.1002/mdc3.14148

Lucchesi M, Biso L, Bonaso M, Longoni B, Buchignani B, Battini R, et al. Mitochondrial dysfunction in genetic and non-genetic Parkinson’s disease. International Journal of Molecular Sciences. 2025;26(9):4451. doi:10.3390/ijms26094451

Gao XY, Yang T, Gu Y, Sun XH. Mitochondrial dysfunction in Parkinson’s disease: From mechanistic insights to therapy. Frontiers in Aging Neuroscience. 2022;14:885500. doi:10.3389/fnagi.2022.885500

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MDS Abstracts - https://www.mdsabstracts.org/abstract/juvenile-onset-parkinsonism-with-bilateral-striatal-necrosis-associated-with-a-pathogenic-mt-nd3-mitochondrial-variant/