Coenzyme Q<sub>10</sub> quantification in muscle, fibroblasts and cerebrospinal fluid by liquid chromatography/tandem mass spectrometry using a novel deuterated internal standard

Duberley, Kate; Hargreaves, Iain P.; Chaiwatanasirikul, Korn-Anong; Heales, Simon; Land, John M.; Rahman, Shamima; Mills, Kevin; Eaton, Simon

doi:10.1002/rcm.6529

Cited by 20 publications

(13 citation statements)

References 40 publications

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“…However, the measurement in muscle may be normal particularly when the deficiency is mild 4. Assessing CoQ10 levels in fibroblasts has been documented to be a reliable method to diagnose CoQ10 deficiency 12 13 15 16. Our results confirm that measuring CoQ10 levels in fibroblasts can be an alternative to muscle measurement.…”

Section: Discussionsupporting

confidence: 79%

“…Significantly reduced activities of MRC enzymes were also observed in fibroblasts. CoQ10 measurement in muscle is the gold standard for diagnosis of CoQ10 deficiency as plasma concentrations of CoQ10 are not reliable and may be influenced by dietary factors 12. However, the measurement in muscle may be normal particularly when the deficiency is mild 4.…”

Section: Discussionmentioning

confidence: 99%

“…CoQ 10 levels were quantified using a tandem mass spectrometer with a 2975 HPLC (Waters, Manchester, UK) as previously described 12. A hexane:ethanol (5:2, v/v) extraction was initially performed and the upper hexane layer was retained for analysis.…”

Section: Methodsmentioning

confidence: 99%

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Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

Liu

Hersheson

Plagnol

et al. 2013

Journal of Neurology, Neurosurgery & Psychiatry

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BackgroundThe autosomal-recessive cerebellar ataxias (ARCA) are a clinically and genetically heterogeneous group of neurodegenerative disorders. The large number of ARCA genes leads to delay and difficulties obtaining an exact diagnosis in many patients and families. Ubiquinone (CoQ10) deficiency is one of the potentially treatable causes of ARCAs as some patients respond to CoQ10 supplementation. The AarF domain containing kinase 3 gene (ADCK3) is one of several genes associated with CoQ10 deficiency. ADCK3 encodes a mitochondrial protein which functions as an electron-transfer membrane protein complex in the mitochondrial respiratory chain (MRC).MethodsWe report two siblings from a consanguineous Pakistani family who presented with cerebellar ataxia and severe myoclonus from adolescence. Whole exome sequencing and biochemical assessment of fibroblasts were performed in the index patient.ResultsA novel homozygous frameshift mutation in ADCK3 (p.Ser616Leufs*114), was identified in both siblings. This frameshift mutation results in the loss of the stop codon, extending the coding protein by 81 amino acids. Significant CoQ10 deficiency and reduced MRC enzyme activities in the index patient's fibroblasts suggested that the mutant protein may reduce the efficiency of mitochondrial electron transfer. CoQ10 supplementation was initiated following these genetic and biochemical analyses. She gained substantial improvement in myoclonic movements, ataxic gait and dysarthric speech after treatment.ConclusionThis study highlights the importance of diagnosing ADCK3 mutations and the potential benefit of treatment for patients. The identification of this new mutation broadens the phenotypic spectrum associated with ADCK3 mutations and provides further understanding of their pathogenic mechanism.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

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Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

Liu

Hersheson

Plagnol

et al. 2013

Journal of Neurology, Neurosurgery & Psychiatry

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“…Furthermore, in view of the purported impermeability of the BBB to CoQ 10 , monitoring of cerebral spinal fluid CoQ 10 levels in preference to those of plasma may be more appropriate in patients with cerebral disease presentations. 93 The possibility arises that the underlying cause of a particular oxidative phosphorylation disorder may dictate the appropriate quinone therapy to implement, whether utilizing CoQ 10 , a synthetic quinone, or a combination of the 2 in the treatment regime. At present however, this information is not available, and studies aimed at establishing these treatment protocols may improve the therapeutic efficacy of quinone supplementation.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Coenzyme Q₁₀ in the Treatment of Mitochondrial Disease

Neergheen

Chalasani

Wainwright

et al. 2017

Journal of Inborn Errors of Metabolism and Screening

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Currently, there is a paucity of available treatment strategies for oxidative phosphorylation disorders. Coenzyme Q 10 (CoQ 10 ) and related synthetic quinones are the only agents to date that have proven to be beneficial in the treatment of these heterogeneous disorders. The therapeutic efficacy of CoQ 10 is not restricted to patients with an underlying CoQ 10 deficiency and is thought to result from its ability to restore electron flow in the mitochondrial respiratory chain (MRC) as well as to increase the cellular antioxidant capacity. At present, however, there is no consensus on the appropriate dosage or therapeutic plasma level of CoQ 10 , and this information will be required before CoQ 10 can be utilized effectively in the treatment of mitochondrial disease. The following review will outline our current knowledge on the use of CoQ 10 in the treatment of MRC disorders and primary CoQ 10 deficiencies.

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“…The concentration of CSF CoQ is in the low nanomolar range and therefore requires specialist analysis by tandem mass spectrometry [59]. Reference ranges have been established for CoQ in CSF, and a suggested application for this technique is in the identification of cerebral CoQ deficiency, although pathological samples were not reported [59]. …”

Section: Coq Determination In Biological Samples What Can We Expect?mentioning

confidence: 99%

The Value of Coenzyme Q10 Determination in Mitochondrial Patients

Yubero

Allen

Artuch

et al. 2017

JCM

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Coenzyme Q10 (CoQ) is a lipid that is ubiquitously synthesized in tissues and has a key role in mitochondrial oxidative phosphorylation. Its biochemical determination provides insight into the CoQ status of tissues and may detect CoQ deficiency that can result from either an inherited primary deficiency of CoQ metabolism or may be secondary to different genetic and environmental conditions. Rapid identification of CoQ deficiency can also allow potentially beneficial treatment to be initiated as early as possible. CoQ may be measured in different specimens, including plasma, blood mononuclear cells, platelets, urine, muscle, and cultured skin fibroblasts. Blood and urinary CoQ also have good utility for CoQ treatment monitoring.

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Coenzyme Q₁₀ quantification in muscle, fibroblasts and cerebrospinal fluid by liquid chromatography/tandem mass spectrometry using a novel deuterated internal standard

Cited by 20 publications

References 40 publications

Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

Coenzyme Q₁₀ in the Treatment of Mitochondrial Disease

The Value of Coenzyme Q10 Determination in Mitochondrial Patients

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Coenzyme Q10 quantification in muscle, fibroblasts and cerebrospinal fluid by liquid chromatography/tandem mass spectrometry using a novel deuterated internal standard

Cited by 20 publications

References 40 publications

Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

Coenzyme Q10 in the Treatment of Mitochondrial Disease

The Value of Coenzyme Q10 Determination in Mitochondrial Patients

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Product

Resources

About

Coenzyme Q₁₀ quantification in muscle, fibroblasts and cerebrospinal fluid by liquid chromatography/tandem mass spectrometry using a novel deuterated internal standard

Coenzyme Q₁₀ in the Treatment of Mitochondrial Disease