General description

Coenzyme Q10 (CoQ10) deficiency is a rare mitochondrial disorder caused by impaired biosynthesis of CoQ10, a lipid-soluble electron carrier in the mitochondrial respiratory chain. This deficiency leads to multisystem manifestations due to disrupted cellular energy production and oxidative stress.

Primary CoQ10 deficiency arises from pathogenic variants in genes involved in CoQ10 biosynthesis, including COQ4, COQ8A, COQ8B, COQ9, and others. These mutations reduce tissue CoQ10 levels, impairing mitochondrial oxidative phosphorylation and increasing reactive oxygen species. The severity of deficiency depends on residual enzyme activity, genetic modifiers, and compensatory mechanisms, leading to clinical heterogeneity.

The disorder presents with variable phenotypes, ranging from neonatal-onset multisystem disease to adult-onset isolated organ involvement. Common features include:

• Neurological: Cerebellar ataxia, seizures, developmental delay, hypotonia, movement disorders, and spastic paraparesis.
• Renal: Steroid-resistant nephrotic syndrome, often progressing to end-stage kidney disease.
• Musculoskeletal: Myopathy, exercise intolerance, and elevated creatine kinase.
• Systemic: Encephalopathy, hepatopathy, and cardiomyopathy in severe infantile forms.

References

1. Wahedi, Azizia, et al. "Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q10 Biosynthesis Disorders." Neurology: Genetics 10.6 (2024): e200209.
2. Münch, Juliane, et al. "Neuroimaging in Primary Coenzyme-Q10-Deficiency Disorders." Antioxidants 12.3 (2023): 718.