Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Pediatric Nephrology
Published in: Pediatric Nephrology 6/2014

01-06-2014 | Review

Primary coenzyme Q10 (CoQ10) deficiencies and related nephropathies

Author: Fatih Ozaltin

Published in: Pediatric Nephrology | Issue 6/2014

Login to get access

Abstract

Oxidative phosphorylation (OXPHOS) is a metabolic pathway that uses energy released by the oxidation of nutrients to generate adenosine triphosphate (ATP). Coenzyme Q10 (CoQ10), also known as ubiquinone, plays an essential role in the human body not only by generating ATP in the mitochondrial respiratory chain but also by providing protection from reactive oxygen species (ROS) and functioning in the activation of many mitochondrial dehydrogenases and enzymes required in pyrimidine nucleoside biosynthesis. The presentations of primary CoQ10 deficiencies caused by genetic mutations are very heterogeneous. The phenotypes related to energy depletion or ROS production may depend on the content of CoQ10 in the cell, which is determined by the severity of the mutation. Primary CoQ10 deficiency is unique among mitochondrial disorders because early supplementation with CoQ10 can prevent the onset of neurological and renal manifestations. In this review I summarize primary CoQ10 deficiencies caused by various genetic abnormalities, emphasizing its nephropathic form.
Literature
1.
2.
McBride HM, Neuspiel M, Wasiak S (2006) Mitochondria: more than just a powerhouse. Curr Biol 16:R551–R560PubMedCrossRef
3.
Chinnery PF, Turnbull DM (2001) Epidemiology and treatment of mitochondrial disorders. Am J Med Genet 106:94–101PubMedCrossRef
4.
Hatefi Y (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 54:1015–1069PubMedCrossRef
5.
6.
7.
8.
Fosslien E (2001) Mitochondrial medicine - Molecular pathology of defective oxidative phosphorylation. Ann Clin Lab Sci 31:25–67PubMed
9.
Balsa E, Marco R, Perales-Clemente E, Szklarczyk R, Calvo E, Landázuri MO, Enríquez JA (2012) NDUFA4 is a subunit of complex IV of the mammalian electron transport chain. Cell Metab 16:378–386PubMedCrossRef
10.
11.
Bentinger M, Brismar K, Dallner G (2007) The antioxidant role of coenzyme Q. Mitochondrion 7[suppl]:S41–S50PubMedCrossRef
12.
13.
Turunen M, Olsson J, Dallner G (2004) Metabolism and function of coenzyme Q. Biochim Biophys Acta 1660(1–2):171–199PubMedCrossRef
14.
Hirsch T, Marzo I, Kroemer G (1997) Role of the mitochondrial permeability transition pore in apoptosis. Biosci Rep 17:67–76PubMedCrossRef
15.
Naderi J, Somayajulu-Nitu M, Mukerji A, Sharda P, Sikorska M, Borowy-Borowski H, Antonsson B, Pandey S (2006) Water-soluble formulation of Coenzyme Q10 inhibits Bax-induced destabilization of mitochondria in mammalian cells. Apoptosis 11:1359–1369PubMedCrossRef
16.
Heeringa SF, Chernin G, Chaki M, Zhou W, Sloan AJ, Ji Z, Xie LX, Salviati L, Hurd TW, Vega-Warner V, Killen PD, Raphael Y, Ashraf S, Ovunc B, Schoeb DS, McLaughlin HM, Airik R, Vlangos CN, Gbadegesin R, Hinkes B, Saisawat P, Trevisson E, Doimo M, Casarin A, Pertegato V, Giorgi G, Prokisch H, Rötig A, Nürnberg G, Becker C, Wang S, Ozaltin F, Topaloglu R, Bakkaloglu A, Bakkaloglu SA, Müller D, Beissert A, Mir S, Berdeli A, Varpizen S, Zenker M, Matejas V, Santos-Ocaña C, Navas P, Kusakabe T, Kispert A, Akman S, Soliman NA, Krick S, Mundel P, Reiser J, Nürnberg P, Clarke CF, Wiggins RC, Faul C, Hildebrandt F (2011) COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness. J Clin Invest 121:2013–2024PubMedCentralPubMedCrossRef
17.
18.
19.
Ogasahara S, Engel AG, Frens D, Mack D (1989) Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy. Proc Natl Acad Sci USA 86:2379–2382PubMedCentralPubMedCrossRef
20.
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 48:1238–1243PubMedCrossRef
21.
Boitier E, Degoul F, Desguerre I, Charpentier C, François 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 156:41–46PubMedCrossRef
22.
Lagier-Tourenne C, Tazir M, López LC, Quinzii CM, Assoum M, Drouot N, Busso C, Makri S, Ali-Pacha L, Benhassine T, Anheim M, Lynch DR, Thibault C, Plewniak F, Bianchetti L, Tranchant C, Poch O, DiMauro S, Mandel JL, Barros MH, Hirano M, Koenig M (2008) ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency. Am J Hum Genet 82:661–672PubMedCentralPubMedCrossRef
23.
Musumeci O, Naini A, Slonim AE, Skavin N, Hadjigeorgiou GL, Krawiecki N, Weissman BM, Tsao CY, Mendell JR, Shanske S, De Vivo DC, Hirano M, DiMauro S (2001) Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology 56:849–855PubMedCrossRef
24.
Quinzii CM, Kattah AG, Naini A, Akman HO, Mootha VK, DiMauro S, Hirano M (2005) Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. Neurology 64:539–541PubMedCrossRef
25.
Lamperti C, Naini A, Hirano M, De Vivo DC, Bertini E, Servidei S, Valeriani M, Lynch D, Banwell B, Berg M, Dubrovsky T, Chiriboga C, Angelini C, Pegoraro E, DiMauro S (2003) Cerebellar ataxia and coenzyme Q10 deficiency. Neurology 60:1206–1208PubMedCrossRef
26.
Gironi M, Lamperti C, Nemni R, Moggio M, Comi G, Guerini FR, Ferrante P, Canal N, Naini A, Bresolin N, DiMauro S (2004) Late-onset cerebellar ataxia with hypogonadism and muscle coenzyme Q10 deficiency. Neurology 62:818–820PubMedCrossRef
27.
Auré K, Benoist JF, Ogier de Baulny H, Romero NB, Rigal O, Lombès A (2004) Progression despite replacement of a myopathic form of coenzyme Q10 defect. Neurology 63:727–729PubMedCrossRef
28.
Mollet J, Delahodde A, Serre V, Chretien D, Schlemmer D, Lombes A, Boddaert N, Desguerre I, de Lonlay P, de Baulny HO, Munnich A, Rötig A (2008) CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures. Am J Hum Genet 82:623–630PubMedCentralPubMedCrossRef
29.
Artuch R, Brea-Calvo G, Briones P, Aracil A, Galván M, Espinós C, Corral J, Volpini V, Ribes A, Andreu AL, Palau F, Sánchez-Alcázar JA, Navas P, Pineda M (2006) Cerebellar ataxia with coenzyme Q10 deficiency: diagnosis and follow-up after coenzyme Q10 supplementation. J Neurol Sci 246:153–158PubMedCrossRef
30.
Le Ber I, Dubourg O, Benoist JF, Jardel C, Mochel F, Koenig M, Brice A, Lombès A, Dürr A (2007) Muscle coenzyme Q10 deficiencies in ataxia with oculomotor apraxia 1. Neurology 68:295–297PubMedCrossRef
31.
D’Arrigo S, Riva D, Bulgheroni S, Chiapparini L, Castellotti B, Gellera C, Pantaleoni C (2008) Ataxia with oculomotor apraxia type 1 (AOA1): clinical and neuropsychological features in 2 new patients and differential diagnosis. J Child Neurol 23:895–900PubMedCrossRef
32.
Gerards M, van den Bosch B, Calis C, Schoonderwoerd K, van Engelen K, Tijssen M, de Coo R, van der Kooi A, Smeets H (2010) Nonsense mutations in CABC1/ADCK3 cause progressive cerebellar ataxia and atrophy. Mitochondrion 10:510–515PubMedCrossRef
33.
Castellotti B, Mariotti C, Rimoldi M, Fancellu R, Plumari M, Caimi S, Uziel G, Nardocci N, Moroni I, Zorzi G, Pareyson D, Di Bella D, Di Donato S, Taroni F, Gellera C (2011) Ataxia with oculomotor apraxia type1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients. Neurogenetics 12:193–201PubMedCrossRef
34.
Pineda M, Montero R, Aracil A, O’Callaghan MM, Mas A, Espinos C, Martinez-Rubio D, Palau F, Navas P, Briones P, Artuch R (2010) Coenzyme Q(10)-responsive ataxia: 2-year treatment follow-up. Mov Disord 25:1262–1268PubMedCrossRef
35.
Horvath R, Czermin B, Gulati S, Demuth S, Houge G, Pyle A, Dineiger C, Blakely EL, Hassani A, Foley C, Brodhun M, Storm K, Kirschner J, Gorman GS, Lochmüller H, Holinski-Feder E, Taylor RW, Chinnery PF (2012) Adult-onset cerebellar ataxia due to mutations in CABC1/ADCK3. J Neurol Neurosurg Psychiatry 83:174–178PubMedCrossRef
36.
Leshinsky-Silver E, Levine A, Nissenkorn A, Barash V, Perach M, Buzhaker E, Shahmurov M, Polak-Charcon S, Lev D, Lerman-Sagie T (2003) Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency. Mol Genet Metab 79:288–293PubMedCrossRef
37.
Quinzii C, Naini A, Salviati L, Trevisson E, Navas P, Dimauro S, Hirano M (2006) A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency. Am J Hum Genet 78:345–349PubMedCentralPubMedCrossRef
38.
Diomedi-Camassei F, Di Giandomenico S, Santorelli FM, Caridi G, Piemonte F, Montini G, Ghiggeri GM, Murer L, Barisoni L, Pastore A, Muda AO, Valente ML, Bertini E, Emma F (2007) COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement. J Am Soc Nephrol 18:2773–2780PubMedCrossRef
39.
Montini G, Malaventura C, Salviati L (2008) Early coenzyme Q10 supplementation in primary coenzyme Q10 deficiency. N Engl J Med 358:2849–2850PubMedCrossRef
40.
Rahman S, Hargreaves I, Clayton P, Heales S (2001) Neonatal presentation of coenzyme Q10 deficiency. J Pediatr 139:456–458PubMedCrossRef
41.
López LC, Schuelke M, Quinzii CM, Kanki T, Rodenburg RJ, Naini A, Dimauro S, Hirano (2006) Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations. Am J Hum Genet 79:1125–1129PubMedCentralPubMedCrossRef
42.
Duncan AJ, Bitner-Glindzicz M, Meunier B, Costello H, Hargreaves IP, López LC, Hirano M, Quinzii CM, Sadowski MI, Hardy J, Singleton A, Clayton PT, Rahman S (2009) A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease. Am J Hum Genet 84:558–566PubMedCentralPubMedCrossRef
43.
Rötig A, Appelkvist EL, Geromel V, Chretien D, Kadhom N, Edery P, Lebideau M, Dallner G, Munnich A, Ernster L, Rustin P (2000) Quinone-responsive multiple respiratory chain dysfunction due to widespread coenzyme Q10 deficiency. Lancet 356:391–395PubMedCrossRef
44.
Mollet J, Giurgea I, Schlemmer D, Dallner G, Chretien D, Delahodde A, Bacq D, de Lonlay P, Munnich A, Rötig A (2007) Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. J Clin Invest 117:765–772PubMedCentralPubMedCrossRef
45.
Di Giovanni S, Mirabella M, Spinazzola A, Di Giovanni S, Mirabella M, Spinazzola A, Crociani P, Silvestri G, Broccolini A, Tonali P, Di Mauro S, Servidei S (2001) Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency. Neurology 57:515–518PubMedCrossRef
46.
Lalani SR, Vladutiu GD, Plunkett K, Lotze TE, Adesina AM, Scaglia F (2005) Isolated mitochondrial myopathy associated with muscle coenzyme Q10 deficiency. Arch Neurol 62:317–320PubMedCrossRef
47.
Horvath R, Schneiderat P, Schoser BG, Gempel K, Neuen-Jacob E, Plöger H, Müller-Höcker J, Pongratz DE, Naini A, DiMauro S, Lochmüller H (2006) Coenzyme Q10 deficiency and isolated myopathy. Neurology 66:253–255PubMedCrossRef
48.
Gempel K, Topaloglu H, Talim B, Schneiderat P, Schoser BG, Hans VH, Pálmafy B, Kale G, Tokatli A, Quinzii C, Hirano M, Naini A, DiMauro S, Prokisch H, Lochmüller H, Horvath R (2007) The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. Brain 130:2037–2044PubMedCrossRef
49.
Emmanuele V, López LC, Berardo A, Naini A, Tadesse S, Wen B, D’Agostino E, Solomon M, DiMauro S, Quinzii C, Hirano M (2012) Heterogeneity of coenzyme Q10 deficiency: patient study and literature review. Arch Neurol 69:978–983PubMedCentralPubMedCrossRef
50.
Salviati L, Sacconi S, Murer L, Zacchello G, Franceschini L, Laverda AM, Basso G, Quinzii C, Angelini C, Hirano M, Naini AB, Navas P, DiMauro S, Montini G (2005) Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: a CoQ10-responsive condition. Neurology 65:606–608PubMedCrossRef
51.
Waldmeier PC, Zimmermann K, Qian T, Tintelnot-Blomley M, Lemasters JJ (2003) Cyclophilin D as a drug target. Curr Med Chem 10:1485–1506PubMedCrossRef
52.
Chretien D, Rustin P, Bourgeron T, Rötig A, Saudubray JM, Munnich A (1994) Reference charts for respiratory chain activities in human tissues. Clin Chim Acta 228:53–70PubMedCrossRef
53.
Rahman S, Clarke CF, Hirano M (2012) 176th ENMC International Workshop: diagnosis and treatment of coenzyme Q10 deficiency. Neuromuscul Disord 22:76–86PubMedCentralPubMedCrossRef
54.
Kirby DM, Thorburn DR, Turnbull DM, Taylor RW (2007) Biochemical assays of respiratory chain complex activity. Methods Cell Biol 80:93–119PubMedCrossRef
55.
Salviati L, Trevisson E, Rodriguez Hernandez MA, Casarin A, Pertegato V, Doimo M, Cassina M, Agosto C, Desbats MA, Sartori G, Sacconi S, Memo L, Zuffardi O, Artuch R, Quinzii C, Dimauro S, Hirano M, Santos-Ocaña C, Navas P (2012) Haploinsufficiency of COQ4 causes coenzyme Q10 deficiency. J Med Genet 49:187–191PubMedCentralPubMedCrossRef
Metadata
Title
Primary coenzyme Q10 (CoQ10) deficiencies and related nephropathies
Author
Fatih Ozaltin
Publication date
01-06-2014
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 6/2014
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-013-2482-z

Other articles of this Issue 6/2014

Pediatric Nephrology 6/2014 Go to the issue

Clinical Quiz

Cyanosis in a male Nigerian infant with acute kidney injury: Answers

Review

Is the renin–angiotensin system actually hypertensive?

Erratum

Erratum to: Renal impairment in children with posterior urethral valves

Original Article

Conversion from twice- to once-daily tacrolimus in pediatric kidney recipients: a pharmacokinetic and bioequivalence study

Original Article

Calcium and vitamin D for osteoprotection in children with new-onset nephrotic syndrome treated with steroids: a prospective, randomized, controlled, interventional study

Obituary

Professor Martin Barratt 1936–2014