To understand the neurodevelopmental trajectories and associations with clinical characteristics in pediatric mitochondrial diseases. 

Developmental delay is common in mitochondrial diseases. However, risk factors associated with poor developmental outcomes are poorly understood. 

We conducted a single-center cohort study of pediatric participants (≤18 years) with a clinical and/or molecular diagnosis of mitochondrial disease. Developmental severity was defined as those with ≥2 domains of developmental delay. We employed descriptive analyses for clinical characteristics and multivariable logistic regression to assess the association between clinical characteristics at disease onset and developmental severity.  

We identified 108 participants in this cohort: female 53%, median age of onset of 1.16 years (IQR 0.55 – 2.52), 82% with a confirmed molecular diagnosis. 60 participants presented critically ill; 33 (47%) in NICU, 27 (41 %) in PICU. Seizures at disease onset (58%) and MRI brain abnormality (79%) were common. Half had EEGs at onset, 83% of which were abnormal, and 62% showed epileptiform discharges. The median follow-up time was 4.11 years (IQR 1.54 – 7.87). Long-termdevelopmental outcomes included gross motor delay (69%), fine motor delay (46%), speech delay (67%), ≥2 domains of developmental delay (66%). Age of onset was associated with ≥2 delays (OR 0.7, 95% CI 0.6 – 0.9, p=0.0001). After adjusting for sex and age of onset, ≥2 delays was associated with abnormal EEG (OR 6.9, 95% CI 1.2 - 43.5, p=0.04), seizures at onset (OR 3.6, 95% CI 1.0 - 18.9, p=0.04), and ICU admission (NICU: OR 4.4, 95% CI 1.0 - 18.9, p=0.04; PICU: OR 4.3, 95% CI 1.0 - 18.0, p=0.046). 

Younger age of onset is a major predictor of developmental outcomes in mitochondrial disease. Nevertheless, there is higher odds of having poorer developmental outcomes with abnormal EEG, seizures, and ICU admission even after adjusting for age of onset and sex.