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Neuropediatrics 2005; 36(3): 214-217
DOI: 10.1055/s-2005-865610
Short Communication

Georg Thieme Verlag KG Stuttgart · New York

Mitochondrial Dysfunction in a Patient with Joubert Syndrome

É. Morava[*] 1 , A. Dinopoulos[*] 2 , H. Y. Kroes3 , R. J. T. Rodenburg1 , H. van Bokhoven4 , L. P. van den Heuvel1 , J. A. M. Smeitink1
  • 1Nijmegen Center for Mitochondrial Disorders, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands
  • 2Cincinnati Children's Hospital Medical Center, Department of Pediatric Neurology, Cincinnati, USA
  • 3University Medical Center Utrecht, Department of Medical Genetics, Utrecht, The Netherlands
  • 4Department of Human Genetics, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands
Further Information

Publication History

Received: January 13, 2005

Accepted after Revision: March 23, 2005

Publication Date:
09 June 2005 (online)

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Abstract

Joubert syndrome is a genetically heterogeneous disorder. The diagnostic criteria include episodic hyperventilation, abnormal eye movements, psychomotor retardation, hypotonia, ataxia, and the characteristic neuro-imaging findings (molar-tooth sign). Many of these clinical features have been observed in new-borns with mitochondrial disorders as well. Congenital brain malformations, including cerebellar hypoplasia, have been described in pyruvate dehydrogenase deficiency. Malformations of the vermis and the cerebellar peduncles, with the lack of axonal decussations, however, are characteristic for Joubert syndrome but unique in patients with mitochondrial disorders. Here, we describe a child with Joubert syndrome presenting with primary lactic acidemia, decreased pyruvate oxidation rates, decreased ATP production, and a mildly decreased pyruvate dehydrogenase complex activity measured in a fresh muscle biopsy. Sequence analysis of the PDHc E1 alpha gene and the PDHX genes revealed no mutations. The patient received continuous feeding through a feeding tube for two years and showed a significant clinical improvement with a complete resolution of the chronic lactic acidemia. A second muscle biopsy revealed significantly decreased pyruvate oxidation rates and ATP production, but a normal pyruvate dehydrogenase complex activity. We suggest that the described mitochondrial dysfunction in our patient is secondary to an underlying mutation leading to Joubert syndrome.

Key words

Joubert syndrome - vermis hypoplasia - lactic acidemia - decreased PDHc activity

References

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1 The authors contributed equally to this work

É. Morava

Radboud University Nijmegen Medical Centre
Department of Pediatrics
Nijmegen Centre for Mitochondrial Disorders

P. O. Box 9101

6500 HB Nijmegen

The Netherlands

Email: E.Morava@cukz.umcn.nl

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