Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2006 Dec;79(6):1125-9.
doi: 10.1086/510023. Epub 2006 Oct 27.

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

Luis Carlos López  1 , Markus Schuelke, Catarina M Quinzii, Tomotake Kanki, Richard J T Rodenburg, Ali Naini, Salvatore Dimauro, Michio Hirano
Affiliations
Case Reports

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

Luis Carlos López et al. Am J Hum Genet. 2006 Dec.

Abstract

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.

PubMed Disclaimer

Figures

Figure  1.
Figure  1.
CoQ10 biosynthetic pathway. Isopentenyl diphosphates derived from the mevalonate pathway generate geranylgeranyl diphosphate. Additional isopentenyl diphosphates are added by decaprenyl diphosphate synthase, which, in humans is a heterotetramer composed of two prenyl diphosphate synthase subunit 1 and two prenyl diphosphate synthase subunit 2 molecules. PHB is derived from the amino acids tyrosine or phenylalanine. After PHB and decaprenyl diphosphate are produced, at least seven enzymes catalyze condensation, methylation, decarboxylation, and hydroxylation reactions to synthesize CoQ10.,
Figure  2.
Figure  2.
A, At age 5 mo, the child was severely hypotonic. B, T2-weighted MR image of the brain at age 3 mo, showing bilateral increased signal intensities at the putamen and globus pallidus, as well as increased white matter signal in the parieto-occipital regions and atrophy in the occipital lobe and peri-insular region. C, EEG during right-sided focal status epilepticus, showing continuous high-voltage 2-hz sharp waves over the entire right hemisphere. D, Gomori trichrome stain, demonstrating several muscle fibers with abnormal subsarcolemmal mitochondrial aggregates (500×). E, COX stain, showing a similar pattern of increased subsarcolemmal stain (400×).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

Web Resource

    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for coenzyme Q10 deficiency, COQ2, PDSS1, COQ3, COQ7, CABC1, APTX, and AOA1)

References

    1. Kawamukai M (2002) Biosynthesis, bioproduction and novel roles of ubiquinone. J Biosci Bioeng 94:511–517 - PubMed
    1. Turunen M, Olsson J, Dallner G (2004) Metabolism and function of coenzyme Q. Biochim Biophys Acta 1660:171–19910.1016/j.bbamem.2003.11.012 - DOI - PubMed
    1. Ogasahara S, Engel AG, Frens D, Mack D (1989) Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy. Proc Natl Acad Sci USA 86:2379–238210.1073/pnas.86.7.2379 - DOI - PMC - PubMed
    1. Sobreira C, Hirano M, Shanske S, Keller RK, Haller RG, Davidson E, Santorelli FM, Miranda AF, Bonilla E, Mojon DS, Barreira AA, King MP, DiMauro S (1997) Mitochondrial encephalomyopathy with coenzyme Q10 deficiency. Neurology 48:1238–1243 - PubMed
    1. Boitier E, Degoul F, Desguerre I, Charpentier C, Francois D, Ponsot G, Diry M, Rustin P, Marsac C (1998) A case of mitochondrial encephalomyopathy associated with a muscle coenzyme Q10 deficiency. J Neurol Sci 156:41–4610.1016/S0022-510X(98)00006-9 - DOI - PubMed

Publication types

MeSH terms