Prevalence and clinical prediction of mitochondrial disorders in a large neuropediatric cohort

Area of Science:

• Pediatric Neurology
• Mitochondrial Genetics
• Clinical Diagnostics

Background:

• Neurological symptoms are common in childhood-onset mitochondrial disorders (MD).
• The precise incidence of MD in general pediatric neurology patients remains unclear.
• Early diagnosis is crucial for timely intervention and management.

Purpose of the Study:

• To determine the incidence of MD in children with neurological symptoms.
• To develop and validate a clinical tool for identifying MD in pediatric patients.
• To improve the early detection of mitochondrial disorders in a clinical setting.

Main Methods:

• A cohort of 491 children with neurological symptoms underwent comprehensive diagnostic evaluation.
• Exome sequencing was utilized for molecular genetic diagnosis.
• A bedside tool, the MDC-NP, was developed and tested for its diagnostic performance.

Main Results:

• A molecular genetic diagnosis was achieved in 51% of the studied children.
• Disease-causing variants in mitochondria-associated genes were identified in 12% of diagnosed cases.
• The MDC-NP demonstrated high diagnostic accuracy with a sensitivity of 0.83 and specificity of 0.96.

Conclusions:

• Mitochondrial disorders are a significant, yet often undiagnosed, cause of neurological symptoms in children.
• The MDC-NP is an effective and accurate tool for the early identification of potential MD cases in neuropediatric settings.
• Implementing the MDC-NP can facilitate earlier diagnosis and management of childhood-onset mitochondrial disorders.