Compound Heterozygous Inheritance of Mutations in Coenzyme Q8A Results in Autosomal Recessive Cerebellar Ataxia and Coenzyme Q10 Deficiency in a Female Sib-Pair

  • Jessie C. Jacobsen
  • Whitney Whitford
  • Brendan Swan
  • Juliet Taylor
  • Donald R. Love
  • Rosamund Hill
  • Sarah Molyneux
  • Peter M. George
  • Richard Mackay
  • Stephen P. Robertson
  • Russell G. SnellEmail author
  • Klaus Lehnert
Research Report
Part of the JIMD Reports book series (JIMD, volume 42)


Autosomal recessive ataxias are characterised by a fundamental loss in coordination of gait with associated atrophy of the cerebellum. There is significant clinical and genetic heterogeneity amongst inherited ataxias; however, an early molecular diagnosis is essential with low-risk treatments available for some of these conditions. We describe two female siblings who presented early in life with unsteady gait and cerebellar atrophy. Whole exome sequencing revealed compound heterozygous inheritance of two pathogenic mutations (p.Leu277Pro, c.1506+1G>A) in the coenzyme Q8A gene (COQ8A), a gene central to biosynthesis of coenzyme Q (CoQ). The paternally derived p.Leu277Pro mutation is predicted to disrupt a conserved motif in the substrate-binding pocket of the protein, resulting in inhibition of CoQ10 production. The maternal c.1506+1G>A mutation destroys a canonical splice donor site in exon 12 affecting transcript processing and subsequent protein translation. Mutations in this gene can result in primary coenzyme Q10 deficiency type 4, which is characterized by childhood onset of cerebellar ataxia and exercise intolerance, both of which were observed in this sib-pair. Muscle biopsies revealed unequivocally low levels of CoQ10, and the siblings were subsequently established on a therapeutic dose of CoQ10 with distinct clinical evidence of improvement after 1 year of treatment. This case emphasises the importance of an early and accurate molecular diagnosis for suspected inherited ataxias, particularly given the availability of approved treatments for some subtypes.


Autosomal recessive cerebellar ataxia CoQ10 COQ8A 



We would like to thank Kristine Boxen at the Auckland Science Analytical Services for Sanger sequencing services and the New Zealand eScience Infrastructure for high-performance computing support.

Supplementary material

475347_1_En_73_MOESM1_ESM.pdf (731 kb)
Supplementary Figure 1 Evolutionary conservation of the locus affected by the missense (PDF 731 kb)
475347_1_En_73_MOESM2_ESM.pdf (85 kb)
Supplementary Tables 1–3 ■■■■ (PDF 85 kb)
475347_1_En_73_MOESM3_ESM.xlsx (24 kb)
Supplementary Table 4 ■■■■ (XLSX 24 kb)
475347_1_En_73_MOESM4_ESM.pdf (65 kb)
Supplementary Methods ■■■■ (PDF 65 kb)


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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2017

Authors and Affiliations

  • Jessie C. Jacobsen
    • 1
  • Whitney Whitford
    • 1
  • Brendan Swan
    • 1
  • Juliet Taylor
    • 2
  • Donald R. Love
    • 3
  • Rosamund Hill
    • 4
  • Sarah Molyneux
    • 6
  • Peter M. George
    • 6
  • Richard Mackay
    • 6
  • Stephen P. Robertson
    • 5
  • Russell G. Snell
    • 1
    Email author
  • Klaus Lehnert
    • 1
  1. 1.Centre for Brain Research, School of Biological SciencesThe University of AucklandAucklandNew Zealand
  2. 2.Genetic Health Service New ZealandAuckland City HospitalAucklandNew Zealand
  3. 3.Diagnostic Genetics, LabPLUSAuckland City HospitalAucklandNew Zealand
  4. 4.Department of NeurologyAuckland City HospitalAucklandNew Zealand
  5. 5.Dunedin School of Medicine, University of OtagoDunedinNew Zealand
  6. 6.Canterbury Health LaboratoriesChristchurchNew Zealand

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