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Some Observations upon Biochemical Causes of Ataxia and a New Disease Entity Ubiquinone, CoQ10 Deficiency

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Abstract

Some hereditary ataxias are treatable and the insight required for this has come from an in depth knowledge of the phenotypes and clinical biochemistry of the conditions. This has required both fundamental and translational clinical research. Prof John Blass was fortunate to begin his career at what we can now recognise as a golden era for such studies and he worked upon two important conditions; Refsum’s disease and Friedreich’s ataxia. More recently the mitochondrial encephalomyopathies have been described and similar investigative work has been undertaken upon them. Ubiquinone, CoQ10, deficiency is the most recently recognised encephalomyopathy and is itself treatable. Though rare, it is becoming increasingly recognised and patients are benefiting from the same scholarly approach to its’ investigation as was afforded Refsums’ disease and Friedreich’s ataxia.

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Authors and Affiliations

  1. Neurometabolic Unit Box 105, National Hospital for Neurology & Neurosurgery, Queen Square, London, WC1N 3BG, UK

    John M. Land, Simon J. R. Heales & Iain P. Hargreaves

  2. Metabolic Unit, Institute of Child Health, Guilford Street, London, WC1N 1EH, UK

    Andrew J. Duncan

Authors
  1. John M. Land
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  2. Simon J. R. Heales
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  3. Andrew J. Duncan
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  4. Iain P. Hargreaves
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Correspondence to John M. Land.

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A dedication to Professor John P. Blass.

Appendix

Appendix

Vignette 1

SA was a lady of 47 years. She had shown psychomotor retardation since early childhood. She was markedly ataxic, unable to walk and requiring a wheelchair or having to bottom shuffle. She also had poor vision and had hypertrophic cardiomyopathy. She was investigated for mitochondrial disease and underwent a muscle biopsy. The results of skeletal muscle respiratory chain enzyme analysis are shown below:

SA

  • Complex I: 0.137 ref interval 0.104–0.268

  • Complex II-III: 0.015 ref interval 0.040–0.204

  • Complex IV: 0.012 ref interval 0.014–0.034

Activities are expressed as a ratio of specific activity to citrate synthase, except for Complex IV, which is expressed as a pseudo first order rate constant relative to citrate synthase. This corrects for mitochondrial enrichment.

The low complex II+III suggested a possible CoQ10 deficiency. This was measured in skeletal muscle as described [37] and confirmed the diagnosis.

Skeletal muscle CoQ10: 33 pmol/mg protein [140-580 pmol/mg of protein] and in isolated mononuclear cells: 20 pmol/mg protein [37–133 pmol/mg protein].

High dose CoQ10 was commenced [300 mg per day]. Over the next six months the patient improved markedly and became able to walk albeit with assistance. A repeat assessment of mononuclear cell CoQ10 was within the reference interval.

111 pmol/mg protein [37–133 pmol/mg protein].

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Land, J.M., Heales, S.J.R., Duncan, A.J. et al. Some Observations upon Biochemical Causes of Ataxia and a New Disease Entity Ubiquinone, CoQ10 Deficiency. Neurochem Res 32, 837–843 (2007). https://doi.org/10.1007/s11064-006-9222-8

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