Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations

Am J Hum Genet. 2006 Dec;79(6):1125-9. doi: 10.1086/510023. Epub 2006 Oct 27.


Coenzyme Q(10) (CoQ(10)) is a vital lipophilic molecule that transfers electrons from mitochondrial respiratory chain complexes I and II to complex III. Deficiency of CoQ(10) has been associated with diverse clinical phenotypes, but, in most patients, the molecular cause is unknown. The first defect in a CoQ(10) biosynthetic gene, COQ2, was identified in a child with encephalomyopathy and nephrotic syndrome and in a younger sibling with only nephropathy. Here, we describe an infant with severe Leigh syndrome, nephrotic syndrome, and CoQ(10) deficiency in muscle and fibroblasts and compound heterozygous mutations in the PDSS2 gene, which encodes a subunit of decaprenyl diphosphate synthase, the first enzyme of the CoQ(10) biosynthetic pathway. Biochemical assays with radiolabeled substrates indicated a severe defect in decaprenyl diphosphate synthase in the patient's fibroblasts. This is the first description of pathogenic mutations in PDSS2 and confirms the molecular and clinical heterogeneity of primary CoQ(10) deficiency.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / genetics*
  • Alkyl and Aryl Transferases / metabolism
  • Biotin / therapeutic use
  • Carnitine / therapeutic use
  • Case-Control Studies
  • Cells, Cultured
  • Coenzymes
  • Fibroblasts / metabolism
  • Humans
  • Infant
  • Kidney Diseases / drug therapy
  • Kidney Diseases / etiology
  • Kidney Diseases / genetics*
  • Leigh Disease / complications
  • Leigh Disease / drug therapy
  • Leigh Disease / genetics*
  • Muscle Hypotonia / genetics
  • Mutation*
  • Protein Subunits
  • Riboflavin / therapeutic use
  • Thiamine / therapeutic use
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / biosynthesis
  • Ubiquinone / deficiency


  • Coenzymes
  • Protein Subunits
  • Ubiquinone
  • Biotin
  • Alkyl and Aryl Transferases
  • decaprenyl pyrophosphate synthetase
  • coenzyme Q10
  • Carnitine
  • Riboflavin
  • Thiamine