Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency.

T Bourgeron; D Chretien; J Poggi-Bach; S Doonan; D Rabier; P Letouzé; A Munnich; A Rötig; P Landrieu; P Rustin

doi:10.1172/JCI117261

INSERM U393, Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France.

Find articles by Bourgeron, T. in: JCI | PubMed | Google Scholar

INSERM U393, Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France.

Find articles by Chretien, D. in: JCI | PubMed | Google Scholar

INSERM U393, Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France.

Find articles by Poggi-Bach, J. in: JCI | PubMed | Google Scholar

INSERM U393, Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France.

Find articles by Doonan, S. in: JCI | PubMed | Google Scholar

INSERM U393, Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France.

Find articles by Rabier, D. in: JCI | PubMed | Google Scholar

INSERM U393, Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France.

Find articles by Letouzé, P. in: JCI | PubMed | Google Scholar

INSERM U393, Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France.

Find articles by Munnich, A. in: JCI | PubMed | Google Scholar

INSERM U393, Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France.

Find articles by Rötig, A. in: JCI | PubMed | Google Scholar

INSERM U393, Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France.

Find articles by Landrieu, P. in: JCI | PubMed | Google Scholar

INSERM U393, Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France.

Find articles by Rustin, P. in: JCI | PubMed | Google Scholar

Published in Volume 93, Issue 6 on June 1, 1994
J Clin Invest. 1994;93(6):2514–2518. https://doi.org/10.1172/JCI117261.
© 1994 The American Society for Clinical Investigation

Published June 1, 1994 - Version history

We report an inborn error of the tricarboxylic acid cycle, fumarase deficiency, in two siblings born to first cousin parents. They presented with progressive encephalopathy, dystonia, leucopenia, and neutropenia. Elevation of lactate in the cerebrospinal fluid and high fumarate excretion in the urine led us to investigate the activities of the respiratory chain and of the Krebs cycle, and to finally identify fumarase deficiency in these two children. The deficiency was profound and present in all tissues investigated, affecting the cytosolic and the mitochondrial fumarase isoenzymes to the same degree. Analysis of fumarase cDNA demonstrated that both patients were homozygous for a missense mutation, a G-955-->C transversion, predicting a Glu-319-->Gln substitution. This substitution occurred in a highly conserved region of the fumarase cDNA. Both parents exhibited half the expected fumarase activity in their lymphocytes and were found to be heterozygous for this substitution. The present study is to our knowledge the first molecular characterization of tricarboxylic acid deficiency, a rare inherited inborn error of metabolism in childhood.

Images.

Version 1 (June 1, 1994): No description

Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency.

T Bourgeron, D Chretien, J Poggi-Bach, S Doonan, D Rabier, P Letouzé, A Munnich, A Rötig, P Landrieu, and P Rustin

Article tools

Metrics

Go to

Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency.

T Bourgeron, D Chretien, J Poggi-Bach, S Doonan, D Rabier, P Letouzé, A Munnich, A Rötig, P Landrieu, and P Rustin

Article tools

Metrics

Go to

Sign up for email alerts