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Review
. 2024 Aug;11(8):948-965.
doi: 10.1002/mdc3.14148. Epub 2024 Jun 28.

Mitochondrial Parkinsonism: A Practical Guide to Genes and Clinical Diagnosis

Piervito Lopriore #  1 , Giovanni Palermo #  2 , Adriana Meli  1 , Gabriele Bellini  1   2 , Elena Benevento  1   2 , Vincenzo Montano  1 , Gabriele Siciliano  1 , Michelangelo Mancuso  1 , Roberto Ceravolo  1   2
Affiliations
Review

Mitochondrial Parkinsonism: A Practical Guide to Genes and Clinical Diagnosis

Piervito Lopriore et al. Mov Disord Clin Pract. 2024 Aug.

Abstract

Background: Primary mitochondrial diseases (PMDs) are the most common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. They can result from mutations in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). These disorders are multisystemic and mainly affect high energy-demanding tissues, such as muscle and the central nervous system (CNS). Among many clinical features of CNS involvement, parkinsonism is one of the most common movement disorders in PMDs.

Methods: This review provides a pragmatic educational overview of the most recent advances in the field of mitochondrial parkinsonism, from pathophysiology and genetic etiologies to phenotype and diagnosis.

Results: mtDNA maintenance and mitochondrial dynamics alterations represent the principal mechanisms underlying mitochondrial parkinsonism. It can be present in isolation, alongside other movement disorders or, more commonly, as part of a multisystemic phenotype. Mutations in several nuclear-encoded genes (ie, POLG, TWNK, SPG7, and OPA1) and, more rarely, mtDNA mutations, are responsible for mitochondrial parkinsonism. Progressive external opthalmoplegia and optic atrophy may guide genetic etiology identification.

Conclusion: A comprehensive deep-phenotyping approach is needed to reach a diagnosis of mitochondrial parkinsonism, which lacks distinctive clinical features and exemplifies the intricate genotype-phenotype interplay of PMDs.

Keywords: mitochondrial parkinsonism; neurogenetics; parkinsonism; primary mitochondrial diseases.

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