Electroclinical correlates of seizures and episodic dystonia in a neonate with primary coenzyme Q10 deficiency due to COQ4 mutations

Primary coenzyme Q10 (CoQ10) deficiency is a rare mitochondrial disorder caused by pathogenic variants in the COQ4 gene. Patients with neonatal onset biallelic COQ4 variants typically present with hypertrophic cardiomyopathy, encephalopathy, hypotonia, seizures, and lactic acidosis. A female neonate born at 38 weeks and 5 days of gestation presented with frequent apneic episodes, early respiratory distress, and hypertrophic cardiomyopathy shortly after birth. Long-term video EEG monitoring revealed electroclinical findings including multifocal refractory seizures, electrographic seizures, involuntary movements, and episodic dystonia. Multiple anti-seizure medications were administered; however, the episodic dystonia persisted. At 22 days of age, the patient was diagnosed with primary CoQ10 deficiency, due to COQ4 mutations. Whole exome sequencing identified compound heterozygous mutations with a maternally inherited missense mutation, c.370G>A, p.(Gly124Ser), and a paternally inherited splicing mutation, c.402+1G>A. Following treatment with high-dose CoQ10, carnitine, and supportive care, the patient demonstrated improved feeding and spontaneous breathing, allowing discontinuation of ventilatory support. However, after transitioning to comfort care, the patient died of respiratory failure. This case highlights the broad neurological phenotype associated with COQ4 -related primary CoQ10 deficiency, presenting with a wide range of symptoms including apnea, multifocal refractory seizures, and notably, abnormal dystonic movements. Episodic dystonia is a rare manifestation, and to date, it has not been reported as a clinical sign in neonatal-onset COQ4 -related disease. Long-term video EEG monitoring helps clarify the differentiation among apnea, dystonic movements, and seizures, facilitating precise treatment in conjunction with CoQ10 supplementation.