Coenzyme Q Deficiency Syndromes - Ubiquinone Deficiency

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

Indications for Testing

Laboratory Testing

  • Serum creatine 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 – gold standard
    • Red, ragged fibers
    • Low fibroblast and/or muscle coenzyme Q levels

Molecular Testing

  • May be helpful, although multiple genes are implicated – refer to tables on genes implicated in primary and secondary coenzyme Q deficiencies in Background section
  • Whole exome or NGS may be best methodology

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 – very rare for primary deficiency
    • Secondary deficiency occurs in mitochondrial disorders
  • 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

  • Majority of patients with deficiency lack a mutation

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
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

Balreira A, Boczonadi V, Barca E, Pyle A, Bansagi B, Appleton M, Graham C, Hargreaves IP, Rasic VM, Lochmüller H, Griffin H, Taylor RW, Naini A, Chinnery PF, Hirano M, Quinzii CM, Horvath R. ANO10 mutations cause ataxia and coenzyme Q₁₀ deficiency J Neurol. 2014; 261(11): 2192-8. PubMed

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

Desbats MA, Lunardi G, Doimo M, Trevisson E, Salviati L. Genetic bases and clinical manifestations of coenzyme Q10 (CoQ 10) deficiency J Inherit Metab Dis. 2015; 38(1): 145-56. PubMed

Emmanuele V, López LC, 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

Ozaltin F. Primary coenzyme Q10 (CoQ 10) deficiencies and related nephropathies Pediatr Nephrol. 2014; 29(6): 961-9. PubMed

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

Quinzii CM, López LC, Naini A, DiMauro S, Hirano M. Human CoQ10 deficiencies. Biofactors. 2008; 32(1-4): 113-8. PubMed

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

Yubero D, Montero R, Armstrong J, Espinós C, Palau F, Santos-Ocaña C, Salviati L, Navas P, Artuch R. Molecular diagnosis of coenzyme Q10 deficiency Expert Rev Mol Diagn. 2015; 15(8): 1049-59. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology

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

Viau KS, Ernst SL, Pasquali M, Botto LD, 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: September 2016