ISSN 2398-2950      

Mitochondrial brain diseases


Mark Lowrie

Laurent Garosi


  • Mitochondria are maternally-inherited cellular organelles located in the cytoplasm of most eukaryotic cells, with the significant exception of erythrocytes. 
  • Also known as the ‘powerhouse’ of the cell as important in energy production. 
  • Mitochondrial diseases are a type of metabolic disorder, involving the respiratory chain which is controlled by both the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). 
  • Tissues with high metabolic demand such as brain, heart, and muscle are more prone to develop dysfunction. 
  • Clinical suspicion of a mitochondrial disease can be raised when in the presence of a progressive history of neurological dysfunction, most commonly in young cats (under 2 years of age) particularly in the face of a multisystemic disorder. 
  • A number of different mitochondrial diseases have been identified in dogs, many with the genetic mutation identified. Only one has been reported in a cat. 
  • Signs: multifocal neurological signs typically in young animals <2 years. 
  • Cause: mutations in mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Usually autosomal recessive mode of inheritance. 
  • Signs: chronic, progressive neurological signs - ataxia, intention tremor, progressive para/tetraparesis, hypermetria, cranial nerve abnormalities, seizures and vestibular signs. 
  • Diagnosis: some genetic tests now available for some of these conditions. For the others, no definitive tests available; CSF and CNS imaging (CT, MRI) can be helpful to rule out other disorders; diagnosis typically made with histopathological evaluation at necropsy; organic acid, amino acid and metabolic pathway testing may be considered on CSF.
  • Treatment: none. 
  • Prognosis: guarded-poor. 



  • Inherited genetic mutations in mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) coding for mitochondrial components, as well as de novo mutations within the individual. 
  • In addition to genetic causes, environmental factors could also play a role in the onset and development of other non-classic mitochondrial disorders. 
  • Furthermore, clinical presentation varies due to heteroplasmy, term describing the presence of mutated and wild-type mtDNA genomes within an individual cell. 
  • Signs of dysfunction typically involve multiple organ systems, however tissues metabolically more active and with high energy requirements such as the nervous system, heart and skeletal muscle are commonly affected. 

Predisposing factors


  • Genetic investigations in the affected cat revealed 2 polymorphisms within the tRNA-Leu(UUR) gene of mitochondrial DNA. One was affecting the Ac Stem loop in the secondary leaf structure of mitochondrial tRNA-Leu, which often is a pathogenic hotspot in humans for mitochondrial encephalopathy. 


  • Clinical signs worsened over 6 months and then euthanasia was performed. 


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Further Reading


Refereed Papers

  • Recent references from PubMed and VetMedResource.
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  • Drögemüller M, Letko A, Matiasek K, Jagannathan V, Corlazzoli D, Rosati M, Jurina K, Medl S, Gödde T, Rupp S, Fischer A (2020) SLC19A3 Loss-of-Function Variant in Yorkshire Terriers with Leigh-Like Subacute Necrotizing Encephalopathy. Genes 11(10), 1215 PubMed.
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