Journal of Inherited Metabolic Disease

, Volume 35, Issue 3, pp 459–467 | Cite as

Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2

  • Emma Glamuzina
  • Ruth Brown
  • Kieran Hogarth
  • Dawn Saunders
  • Isabelle Russell-Eggitt
  • Matthew Pitt
  • Carlos de Sousa
  • Shamima Rahman
  • Garry Brown
  • Stephanie Grunewald
Original Article


Pontocerebellar hypoplasia type 6 (PCH6) (MIM #611523) is a recently described disorder caused by mutations in RARS2 (MIM *611524), the gene encoding mitochondrial arginyl-transfer RNA (tRNA) synthetase, a protein essential for translation of all mitochondrially synthesised proteins. This case confirms that progressive cerebellar and cerebral atrophy with microcephaly and complex epilepsy are characteristic features of PCH6. Additional features of PCH subtypes 2 and 4, including severe dystonia, optic atrophy and thinning of the corpus callosum, are demonstrated. Congenital lactic acidosis can be present, but respiratory chain dysfunction may be mild or absent, suggesting that disordered mitochondrial messenger RNA (mRNA) translation may not be the only mechanism of impairment or that a secondary mechanism exists to allow some translation. We report two novel mutations and expand the phenotypic spectrum of this likely underdiagnosed PCH variant, where recognition of the characteristic neuroradiological phenotype could potentially expedite genetic diagnosis and limit invasive investigations.


Optic Atrophy Respiratory Chain Enzyme Congenital Muscular Dystrophy Sort Intolerant From Tolerant Anticodon Loop 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We acknowledge our patient’s family for allowing us to publish her medical information and MRI images. Shamima Rahman is funded by Great Ormond Street Hospital Children’s Charity.

Supplementary material

10545_2011_9413_MOESM1_ESM.doc (95 kb)
Supplementary Figure 1 (DOC 95 kb)


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Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  • Emma Glamuzina
    • 1
    • 8
  • Ruth Brown
    • 2
  • Kieran Hogarth
    • 6
  • Dawn Saunders
    • 6
  • Isabelle Russell-Eggitt
    • 5
  • Matthew Pitt
    • 3
  • Carlos de Sousa
    • 4
  • Shamima Rahman
    • 1
    • 7
  • Garry Brown
    • 2
  • Stephanie Grunewald
    • 1
    • 7
  1. 1.Department of Metabolic MedicineGreat Ormond Street Hospital for ChildrenLondonUK
  2. 2.Department of BiochemistryUniversity of OxfordOxfordUK
  3. 3.Department of NeurophysiologyGreat Ormond Street Hospital for ChildrenLondonUK
  4. 4.Department of NeurologyGreat Ormond Street Hospital for ChildrenLondonUK
  5. 5.Department of Ophthalmology, Ulverscroft Vision Research GroupGreat Ormond Street Hospital for ChildrenLondonUK
  6. 6.Department of RadiologyGreat Ormond Street Hospital for ChildrenLondonUK
  7. 7.UCL Institute of Child HealthUniversity College LondonLondonUK
  8. 8.National Metabolic ServiceStarship Children’s HospitalAucklandNew Zealand

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