Coenzyme Q Deficiency Syndromes - Ubiquinone Deficiency

  • Diagnosis
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

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
  • Serum coenzyme Q levels used for monitoring of therapy

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

Creatine Kinase, Total, Serum or Plasma 0020010
Method: Quantitative Enzymatic

Limitations

Not specific for coenzyme Q deficiency

Creatine Kinase Isoenzymes 0020414
Method: Quantitative Enzymatic/Electrophoresis

Limitations

Not specific for coenzyme Q deficiency

Lactic Acid, Plasma 0020045
Method: Enzymatic

Coenzyme Q10, Total 0081119
Method: Quantitative High Performance Liquid Chromatography

Limitations

Not useful in coenzyme Q deficiency diagnosis

General References

Carrozzo R, Piemonte F, Tessa A, Lucioli S, Rizza T, Meschini M, Fattori F, Santorelli F. Infantile mitochondrial disorders. Biosci Rep. 2007; 27(1-3): 105-12. PubMed

Emmanuele V, López L, López L, Berardo A, Naini A, Tadesse S, Wen B, D'Agostino E, Solomon M, DiMauro S, Quinzii C, Hirano M. Heterogeneity of coenzyme Q10 deficiency: patient study and literature review. Arch Neurol. 2012; 69(8): 978-83. PubMed

Montero R, Pineda M, Aracil A, Vilaseca M, Briones P, Sánchez-Alcázar J, Navas P, Artuch R. Clinical, biochemical and molecular aspects of cerebellar ataxia and Coenzyme Q10 deficiency. Cerebellum. 2007; 6(2): 118-22. PubMed

Quinzii C, Hirano M. Primary and secondary CoQ(10) deficiencies in humans. Biofactors. 2011; 37(5): 361-5. PubMed

Steele P, Tang P, DeGrauw A, Miles M. Clinical laboratory monitoring of coenzyme Q10 use in neurologic and muscular diseases. Am J Clin Pathol. 2004; 121 Suppl: S113-20. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology

Lu J, Frank E. Measurement of coenzyme Q10 in clinical practice. Clin Chim Acta. 2007; 384(1-2): 180-1. PubMed

Viau K, Ernst S, Pasquali M, Botto L, Hedlund G, Longo N. Evidence-based treatment of guanidinoacetate methyltransferase (GAMT) deficiency. Mol Genet Metab. 2013; 110(3): 255-62. PubMed

Medical Reviewers

Last Update: December 2015