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Neuropediatrics 2005; 36(3): 193-199
DOI: 10.1055/s-2005-865713
Original Article

Georg Thieme Verlag KG Stuttgart · New York

Neonatal Lactic Acidosis, Complex I/IV Deficiency, and Fetal Cerebral Disruption

H. L. M. van Straaten1 , J. P. van Tintelen2 , J. M. F. Trijbels3 , L. P. van den Heuvel3 , D. Troost4 , J. M. Rozemuller4 , M. Duran5 , L. S. de Vries6 , M. Schuelke7 , P. G. Barth8
  • 1Neonatal Intensive Care Unit, Isala Clinics, Zwolle, The Netherlands
  • 2Department of Clinical Genetics, University Hospital Groningen, Groningen, The Netherlands
  • 3Department of Pediatrics, University Medical Center St Radboud, Nijmegen, The Netherlands
  • 4Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • 5Department of Pediatrics, Emma Children's Hospital and Laboratory of Genetic Metabolic Diseases, AMC, University of Amsterdam, Amsterdam, The Netherlands
  • 6Neonatal Intensive Care Unit, Wilhelmina Children's Hospital, University of Utrecht, Utrecht, The Netherlands
  • 7Klinik für Pädiatrie mit Schwerpunkt Neurologie, Charité Campus Virchow-Klinikum, Berlin, Germany
  • 8Department of Pediatric Neurology, Emma Children's Hospital/AMC, University of Amsterdam, Amsterdam, The Netherlands
Further Information

Publication History

Received: August 30, 2004

Accepted after Revision: May 1, 2005

Publication Date:
09 June 2005 (online)

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Abstract

Cerebral developmental abnormalities occur in various inborn errors of metabolism including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and others. Associations with abnormalities of the respiratory chain are rare. Here we report male and female siblings with microcephaly, a complex neuromigrational disorder including ependymal cysts, leptomeningeal and subcortical heterotopia, polymicrogyria, multifocal cerebral calcifications, agenesis of the corpus callosum, and spongiform changes in brainstem and cerebellum. Intractable lactic acidosis, causing death on the first day of life, was associated with severely reduced activities of complex I and complex IV. The neuropathological and biochemical findings are closely similar to those reported previously by Samsom et al. in 1994. The findings confirm a distinct genetic syndrome of disrupted brain development with TORCH-like calcifications, and a complex neuronal migration disorder associated with a multicomplex disorder of the respiratory chain.

Key words

Cerebral calcifications - respiratory chain defects - corpus callosum agenesis - neuronal heterotopia - leptomeningeal heterotopia - ependymal cysts - microcephaly - congenital infection

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Prof. M. D. Peter G. Barth

Department of Pediatric Neurology
Emma Children's Hospital/AMC

P.O. Box 22700

1100 DD Amsterdam

The Netherlands

Email: p.g.barth@amc.uva.nl

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