Related Experiment Video
Updated: Mar 15, 2026
Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes
Published on: October 10, 2025
Myoclonus epilepsy in mitochondrial disorders
Costanza Lamperti1, Massimo Zeviani2
1Unit of Molecular Neurogenetics, The Carlo Besta Institute of Neurology, Milan, Italy.
Abstract:
Mitochondrial disorders is a group of clinical entities associated with abnormalities of the mitochondrial respiratory chain (MRC), which carries out the oxidative phosphorylation (OXPHOS) of ADP into ATP. As the MRC is the result of genetic complementation between two separate genomes, nuclear and mitochondrial, OXPHOS failure can derive from mutations in either nuclear-encoded, or mitochondrial-encoded, genes. Epilepsy is a relatively common feature of mitochondrial disease, especially in early-onset encephalopathies of infants and children. However, the two most common entities associated with epilepsy include MERRF, for Myoclonic Epilepsy with Ragged Red Fibers, and AHS, or Alpers-Huttenlocher syndrome, also known as hepatopathic poliodystrophy. Whilst MERRF is a maternally inherited condition caused by mtDNA mutations, particularly the 8344A>G substitution in the gene encoding mt-tRNALys, AHS is typically caused by recessive mutations in POLG, encoding the catalytic subunit of polymerase gamma, the only mtDNA polymerase in humans. AHS is the most severe, early-onset, invariably fatal syndrome within a disease spectrum, which also include other epileptogenic entities, all due to POLG mutations and including Spino-cerebellar Ataxia and Epilepsy (SCAE). This review reports the main clinical, neuroimaging, biochemical, and molecular features of epilepsy-related mitochondrial syndrome, particularly MERRF and AHS.
Insights
Mitochondrial disorders can cause epilepsy, particularly in infants. This review focuses on Myoclonic Epilepsy with Ragged Red Fibers (MERRF) and Alpers-Huttenlocher syndrome (AHS), common mitochondrial diseases presenting with seizures.
Area of Science:
- Mitochondrial Medicine
- Neurogenetics
- Biochemistry
Background:
- Mitochondrial disorders stem from defects in the mitochondrial respiratory chain (MRC), impacting ATP production via oxidative phosphorylation (OXPHOS).
- Epilepsy is a frequent symptom, especially in early-onset mitochondrial encephalopathies.
- Myoclonic Epilepsy with Ragged Red Fibers (MERRF) and Alpers-Huttenlocher syndrome (AHS) are key epilepsy-associated mitochondrial diseases.
Purpose of the Study:
- To review the clinical, neuroimaging, biochemical, and molecular characteristics of epilepsy-related mitochondrial syndromes.
- To highlight the specific features of MERRF and AHS.
- To elucidate the genetic basis of these conditions.
Main Methods:
- Literature review of epilepsy-related mitochondrial disorders.
- Analysis of clinical presentations, neuroimaging findings, biochemical markers, and genetic mutations.
- Focus on MERRF (mtDNA mutations) and AHS (POLG mutations).
Main Results:
- MERRF is characterized by maternally inherited mtDNA mutations, often the 8344A>G substitution.
- AHS, a severe early-onset fatal syndrome, is typically caused by recessive POLG mutations.
- POLG mutations are associated with a spectrum of epileptogenic disorders, including Spino-cerebellar Ataxia and Epilepsy (SCAE).
Conclusions:
- Mitochondrial disorders represent a significant cause of epilepsy, particularly in pediatric populations.
- Understanding the genetic underpinnings of MERRF and AHS is crucial for diagnosis and management.
- Further research into mitochondrial disease mechanisms can improve therapeutic strategies.
Related Concept Videos
01:13Seizures: Classification
Seizures are typically classified into two main categories: focal and generalized seizures.
Focal Seizures
Focal seizures originate from specific regions of the brain. These seizures are further sub-classified into two types:
01:24Epilepsy and Seizures: Overview
Various factors can trigger epilepsy, including genetic factors, brain damage, metabolic causes, and unknown etiology. Diagnosis of epilepsy involves electroencephalography (EEG), which...
01:28Disorders of the Skeletal Muscle
Musculoskeletal disorders
Musculoskeletal disorders involve injuries and conditions affecting the skeletal muscles and associated connective tissues. These disorders can arise from acute biomechanical stresses or chronic overuse and can occur across different age groups. Common injuries include sprains, fractures, and muscular strains, often resulting from...
02:59Animal Mitochondrial Genetics
01:14Antiepileptic Drugs: Glutamate Antagonists
01:48ATP Synthase: Mechanism