Coenzyme Q Deficiency Syndromes - Ubiquinone Deficiency

Diagnosis

Indications for Testing

• Clinical presentation similar to mitochondrial disorders or metabolic disorders with negative results in testing for these disorders

Laboratory Testing

• Serum creatinine kinase and lactic acid levels
  • Elevated in myopathic forms
  • Normal in cerebellar ataxic forms
• Serum coenzyme Q testing – not useful in diagnosis (see Monitoring)

Histology

• Muscle biopsy
  • Red, ragged fibers
  • Low fibroblast/muscle coenzyme Q levels

Differential Diagnosis

• Mitochondrial diseases
• Muscular dystrophy
• Metabolic disorders
• Friedreich ataxia

Monitoring

Clinical Background

Coenzyme Q (ubiquinone) deficiency has been associated with a variety of diseases that include infantile as well as adult forms (uncommon).

Epidemiology

• Incidence – rare
• Age – most disorders present during infancy
• Sex – M:F, equal

Inheritance

• Autosomal recessive with variable phenotypes
  • Cerebellar ataxia – most common form 
  • Encephalomyopathy
  • Severe infantile multisystemic disease
  • Leigh syndrome
  • Isolated myopathy

Genetics

• COQ2, PDSS1, PDSS2 mutations cause severe infantile forms

Pathophysiology

• Coenzyme Q synthesized in the mitochondrial inner membrane and transports electrons in the mitochondria – essential for mitochondrial respiration
• Coenzyme Q is also an antioxidant – prevents progression of lipid peroxidation in membranes
• Affected patients have a deficiency in one of the enzymes needed to synthesize coenzyme Q

Clinical Presentation

• Cerebellar ataxia  – ataxia, cerebellar atrophy, hypogonadism, seizures, developmental delay
• Infantile forms
  • Musculoskeletal – generalized proximal muscle weakness, myopathy, myoglobinuria
  • Neurologic – seizures, progressive ataxia, cognitive impairment
  • Ophthalmologic – retinitis pigmentosa, optic nerve atrophy, nystagmus, myopia
  • Renal – nephritic syndrome causing renal failure
• Leigh syndrome – necrotizing encephalopathy with vision loss, failure to thrive, and liver failure
• Myopathy – muscle weakness; may have adult onset
• Encephalomyopathy – myoglobinuria, brain involvement

Treatment

• Oral coenzyme Q supplementation

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory