Description:
Coenzyme Q serves as a redox carrier in the mitochondrial respiratory chain and is a lipid-soluble antioxidant. CoQ10 transfers reducing equivalents from various dehydrogenases to complex III (ubiquinone cytochrome c reductase) and acts as a transmembrane hydrogen carrier. Primary coenzyme Q10 deficiency is a rare, clinically heterogeneous autosomal recessive disorder with 3 major clinical presentations: (1) an encephalomyopathic form, characterized by exercise intolerance, mitochondrial myopathy, myoglobinuria, epilepsy, and ataxia; (2) a generalized infantile variant with severe encephalopathy and renal disease; and (3) an ataxic form, dominated by ataxia, seizures, cerebral atrophy, and/or anomalies of the basal ganglia. Q10 deficiency can be caused by mutations in mitochondrial parahydroxybenzoate-polyprenyltransferase (COQ2), prenyl diphosphate synthase, subunit 1(PDSS1), prenyl diphosphate synthase, subunit 2 (PDSS2), and APTX gene. COQ2 catalyzes one of the final reactions in the biosynthesis of CoQ, the prenylation of parahydroxybenzoate with an all-trans polyprenyl group. If there is biochemical evidence of Q10 deficiency or complex III deficiency, DNA analysis of the relevant genes can be performed to confirm the diagnosis. COQ2 gene maps to chromosome 4q21-q22, and contains 7 exons.

Reasons for Referral:

• Confirmation of a clinical diagnosis
• Carrier testing
• Prenatal diagnosis for known familial mutations

Testing Methodology:
The exons and flanking intronic regions of the COQ2 gene are PCR amplified and sequenced in both the forward and reverse directions.

Specimen Requirements:
Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc
Requisition form must accompany the specimen. To receive forms, additional information or specimen collection kits, please contact the laboratory. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:
Index: 4 weeks
Known Familial Mutation: 2 weeks

CPT Codes and Prices:
Index: 83891, 83904x14, 83898x7, 83912, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

Shipping Information

Forms:
 >> Gene Sequencing Requisition or Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included
 >> Prenatal Requisition

References:
1. Quinzii C, Naini A, Salviati L, et al. A Mutation in Para-Hydroxybenzoate-Polyprenyl Transferase (COQ2) Causes Primary Coenzyme Q10 Deficiency. Am. J. Hum. Genet. 2006; 78:345–349.

2. Forsgren M, Attersand A, Lake S, GR¨Unler J, et al. Climent IIsolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ. Biochem. J. 2004; 382, 519–526,

3. Mollet J, Giurgea I, Schlemmer D, et al. Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. J. Clin. Invest. 2007; 117:765–772.

4. López-Martín JM, Salviati L, Trevisson E, et al. Missense mutation of the COQ2 gene causes defects of bioenergetics and de novo pyrimidine synthesis. Hum Mol Genet. 2007; 16(9):1091-7.

Test Codes:
Index: 3415
Known Familial Mutation: 3416
Prenatal: 3417

Last Modified: 5-13-08