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. The isoprenoid chain of Q10 varies in length between species and is determined by prenyl diphosphate synthase. 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. Both PDSS1 and PDSS2 are required for the generation of prenyl diphosphate synthase. Humans possess a heterotetrameric prenyl diphosphate synthase composed of PDSS1 and PDSS2 gene products that produces Q10. Mutations in PDSS2 gene have been reported causing primary CoQ10 deficiency in an infant with fatal Leigh syndrome and nephrotic syndrome. 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. PDSS2 gene maps to chromosome 6q21. It contains 8 exons and encodes for a protein of 399 amino acids.

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 PDSS2 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, 83904x16, 83898x8, 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. Lopez LC, Schuelke M, Quinzii CM, et al. Leigh Syndrome with Nephropathy and CoQ10 Deficiency Due to decaprenyl diphosphate synthase subunit 2 (PDSS2) Mutations. Am. J. Hum. Genet. 2006; 79:1125–1129.

2. Saiki R, Nagata A, Kainou T, et al. Characterization of solanesyl and decaprenyl diphosphate synthases in mice and humans. FEBS J. 2005; 272: 5606-5622.

3. Quinzii CM, López LC, Von-Moltke J, et al. Respiratory chain dysfunction and oxidative stress correlate with severity of primary CoQ10 deficiency. FASEB J. 2008. [Epub ahead of print]

4. Quinzii CM, Hirano M, DiMauro S. CoQ10 deficiency diseases in adults. Mitochondrion. 2007; 7; Suppl:S122-6.

Test Codes:
Index: 3410
Known Familial Mutation: 3411
Prenatal: 3412

Last Modified: 5-13-08