Mitochondrial dysfunction in a patient with Joubert syndrome

Eva Morava-Kozicz, A. Dinopoulos, H. Y. Kroes, R. J.T. Rodenburg, H. Van Bokhoven, L. P. Van Den Heuvel, J. A.M. Smeitink

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)214-217
Number of pages4
JournalNeuropediatrics
Volume36
Issue number3
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

Fingerprint

Pyruvate Dehydrogenase Complex
Mitochondrial Diseases
Pyruvic Acid
Milk
Pyruvate Dehydrogenase Complex Deficiency Disease
Adenosine Triphosphate
Biopsy
Muscles
Mutation
Muscle Hypotonia
Hyperventilation
Dyskinesias
Enteral Nutrition
Ataxia
Eye Movements
Genes
Sequence Analysis
Tooth
Joubert syndrome 1
Brain

Keywords

  • Decreased PDHc activity
  • Joubert syndrome
  • Lactic acidemia
  • Vermis hypoplasia

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

Morava-Kozicz, E., Dinopoulos, A., Kroes, H. Y., Rodenburg, R. J. T., Van Bokhoven, H., Van Den Heuvel, L. P., & Smeitink, J. A. M. (2005). Mitochondrial dysfunction in a patient with Joubert syndrome. Neuropediatrics, 36(3), 214-217. https://doi.org/10.1055/s-2005-865610

Mitochondrial dysfunction in a patient with Joubert syndrome. / Morava-Kozicz, Eva; Dinopoulos, A.; Kroes, H. Y.; Rodenburg, R. J.T.; Van Bokhoven, H.; Van Den Heuvel, L. P.; Smeitink, J. A.M.

In: Neuropediatrics, Vol. 36, No. 3, 01.06.2005, p. 214-217.

Research output: Contribution to journalArticle

Morava-Kozicz, E, Dinopoulos, A, Kroes, HY, Rodenburg, RJT, Van Bokhoven, H, Van Den Heuvel, LP & Smeitink, JAM 2005, 'Mitochondrial dysfunction in a patient with Joubert syndrome', Neuropediatrics, vol. 36, no. 3, pp. 214-217. https://doi.org/10.1055/s-2005-865610
Morava-Kozicz E, Dinopoulos A, Kroes HY, Rodenburg RJT, Van Bokhoven H, Van Den Heuvel LP et al. Mitochondrial dysfunction in a patient with Joubert syndrome. Neuropediatrics. 2005 Jun 1;36(3):214-217. https://doi.org/10.1055/s-2005-865610
Morava-Kozicz, Eva ; Dinopoulos, A. ; Kroes, H. Y. ; Rodenburg, R. J.T. ; Van Bokhoven, H. ; Van Den Heuvel, L. P. ; Smeitink, J. A.M. / Mitochondrial dysfunction in a patient with Joubert syndrome. In: Neuropediatrics. 2005 ; Vol. 36, No. 3. pp. 214-217.
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