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CLINICAL CHARACTERISTICS: Primary coenzyme Q10 (CoQ10) deficiency is usually associated with multisystem involvement, including neurologic manifestations such as fatal neonatal encephalopathy with hypotonia; a late-onset slowly progressive multiple-system atrophy-like phenotype (neurodegeneration with autonomic failure and various combinations of parkinsonism and cerebellar ataxia, and pyramidal dysfunction); and dystonia, spasticity, seizures, and intellectual disability. Steroid-resistant nephrotic syndrome (SRNS), the hallmark renal manifestation, is often the initial manifestation either as isolated renal involvement that progresses to end-stage renal disease (ESRD), or associated with encephalopathy (seizures, stroke-like episodes, severe neurologic impairment) resulting in early death. Hypertrophic cardiomyopathy (HCM), retinopathy or optic atrophy, and sensorineural hearing loss can also be seen. DIAGNOSIS/TESTING: The diagnosis of primary CoQ10 deficiency in a proband is established by identification of biallelic pathogenic variants in one of the nine genes encoding proteins directly involved in the synthesis of coenzyme Q10 or by detection of reduced levels of CoQ10 (ubiquinone) in skeletal muscle or reduced activities of complex I+III and II+III of the mitochondrial respiratory chain on frozen muscle homogenates. MANAGEMENT: Treatment of manifestations: In individuals with primary CoQ10 deficiency early treatment with high-dose oral CoQ10 supplementation (ranging from 5 to 50 mg/kg/day) can limit disease progression and reverse some manifestations; however, established severe neurologic and/or renal …