Related Experiment Video
Updated: Aug 3, 2025
An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model
Published on: March 9, 2022
Phenotyping mitochondrial DNA-related diseases in childhood: A cohort study of 150 patients
Anna Ardissone1, Giulia Ferrera1, Costanza Lamperti2
1Child Neurology Unit, Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Insights
Mitochondrial DNA (mtDNA) defects are less common than nuclear DNA (nDNA) defects in pediatric mitochondrial diseases (MDs). This study highlights frequent ocular involvement and identifies prognostic factors in children with mtDNA-related disorders.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Mitochondrial diseases (MDs) are complex genetic disorders arising from mutations in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA).
- Pediatric MDs often present with heterogeneous phenotypes, complicating diagnosis and management.
- Existing research frequently overlooks the distinction between nDNA- and mtDNA-related MDs, and lacks large cohort studies focused on pediatric mtDNA defects.
Approach:
- A retrospective analysis was conducted on the clinical, metabolic, biochemical, and neuroimaging data of 150 pediatric patients diagnosed with MDs due to mtDNA alterations.
- Data were collected over a 20-year period from a specialized neurological institute.
Key Points:
- Mitochondrial DNA (mtDNA) impairment is less frequent than nDNA impairment in pediatric MDs.
- Ocular involvement, including Leber hereditary optic neuropathy, is highly prevalent, particularly in children under 12.
- Deep gray matter involvement, early onset, Pearson syndrome, and Leigh syndrome are associated with poor prognosis.
- Single large-scale mtDNA deletions are common in pediatric cases.
- A novel association between an mtDNA pathogenic variant and cavitating leukodystrophy is reported.
Conclusions:
- This study provides valuable insights into the phenotypical spectrum of pediatric mtDNA defects.
- Findings offer guidance for the diagnostic workup and therapeutic strategies for children with these rare disorders.
Background And Purpose:
Mitochondrial diseases (MDs) are heterogeneous disorders caused by mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) associated with specific syndromes. However, especially in childhood, patients often display heterogeneity. Several reports on the biochemical and molecular profiles in children have been published, but studies tend not to differentiate between mtDNA- and nDNA-associated diseases, and focus is often on a specific phenotype. Thus, large cohort studies specifically focusing on mtDNA defects in the pediatric population are lacking.
Methods:
We reviewed the clinical, metabolic, biochemical, and neuroimaging data of 150 patients with MDs due to mtDNA alterations collected at our neurological institute over the past 20 years.
Results:
mtDNA impairment is less frequent than nDNA impairment in pediatric MDs. Ocular involvement is extremely frequent in our cohort, as is classical Leber hereditary optic neuropathy, especially with onset before 12 years of age. Extraneurological manifestations and isolated myopathy appear to be rare, unlike adult phenotypes. Deep gray matter involvement, early disease onset, and specific phenotypes, such as Pearson syndrome and Leigh syndrome, represent unfavorable prognostic factors. Phenotypes related to single large scale mtDNA deletions appear to be very frequent in the pediatric population. Furthermore, we report for the first time an mtDNA pathogenic variant associated with cavitating leukodystrophy.
Conclusions:
We report on a large cohort of pediatric patients with mtDNA defects, adding new data on the phenotypical characterization of mtDNA defects and suggestions for diagnostic workup and therapeutic approach.
Related Concept Videos
02:59Animal Mitochondrial Genetics
01:35Pedigree Analysis
01:37Mitochondria