COQ2 mutations cause the most variable clinical phenotype among primary CoQ10 deficiencies, with onset varying from the neonatal period up to the seventh decade of life.
Three main phenotypes that have been associated with COQ2 mutations:
- A severe, rapidly progressive multisystemic disorder with neonatal onset and manifesting with encephalopathy, nephropathy and hypertrophic cardiomyopathy, rapidly evolving to multiorgan failure (including liver disease).
- A childhood onset renal disease characterized by steroid-resistant nephrotic syndrome (SRNS), initially manifesting with proteinuria that, if untreated, rapidly evolves to end stage renal failure. SRNS is variably associated with encephalopathy (with one or more of the following: epilepsy, dystonia, developmental delay, hypotonia, myoclonus, nystagmus, stroke-like lesions, tremor, cerebellar atrophy), and visual impairment (with retinitis, optic nerve atrophy or retinitis pigmentosa). A milder disease with a later onset of a slowly progressive SRNS and mild neurological symptoms has been reported.
- An adult onset (usually in the 6°-7° decade of life) neurological disease resembling multiple system atrophy with retinopathy, without renal involvement.