Biallelic pathogenic variants in COQ4cause primary coenzyme Q10 (CoQ10) deficiency type 7 (COQ10D7). COQ4encodes a protein that is essential for the biosynthesis of coenzyme Q10, a key component of the mitochondrial respiratory chain. The disorder is very rare; fewer than 100 patients have been reported worldwide. Inheritance is autosomal recessive.
The clinical spectrum is broad. Three general presentations can be recognized: (1) a severe early-onset (prenatal/neonatal) form with hypotonia, respiratory insufficiency, cardiomyopathy, epileptic encephalopathy and cerebellar hypoplasia, often fatal in the first months of life; (2) an intermediate childhood-onset form with encephalopathy and stroke-like episodes; and (3) a milder, later-onset form with slowly progressive spinocerebellar ataxia and/or spastic paraparesis.
Not all individuals with COQ4variants have all of these features.