Background: Mitochondrial disease is a heterogeneous disorder that is caused by numerous different gene mutations and may present with variable clinical phenotypes. As whole exome sequencing becomes more affordable and feasible in clinical practice, more novel gene mutations that leading to this disease can be identified.

Method: Trio whole-exome sequencing was performed in a cohort of 15 patients with clinically suspected early-onset (infantile onset) mitochondrial disease. Detailed genetic and clinical data were collected.

Result: We identified CoQ4 homozygous c.370G>A mutation in 2 siblings. Subject 1 is a male, currently 8 years of age and subject 2 is a female, currently 2 years of age. Their parents carried heterozygous c.370G>A mutation. Both the subjects had similar clinical presentations. They presented with developmental arrest, epileptic encephalopathy, cardiomyopathy and gastroesophageal reflux since the age of 3 months. Brain MRI showed paper-thin corpus callosum and brain atrophy. Currently, both had refractory epilepsy, severe hypotonia and were bed-ridden. Both serum baseline CoQ10 level were decreased, while increased after supplementation of high-dose CoQ10.

Conclusion: COQ4 mutations cause early-onset mitochondrial diseases that are associated with CoQ10 deficiency. They might benefit from high-dose CoQ10 supplementation.