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Familial mitochondrial encephalopathy with fetal ultrasonographic ventriculomegaly and intracerebral calcifications

  • Neuropediatrics
  • Original Paper
  • Published:
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Abstract

In two sibs antenatal ultrasonography revealed identical intracranial calcification, ventricular widening and microcephaly. The first pregnancy was artificially terminated at 19 weeks. Post-mortem examination of the brain revealed destructive calcification and extracerebral neuronal heterotopia. The second sib went to term but died 48 h after birth from irreversible lactic acidosis. Autopsy showed extensive encephalopathy with cavitation and calcification in the cerebral hemispheres, polymicrogyria, multiple neuronal heterotopia, partial callosal dysgenesis, and severe Leigh syndrome, together forming a continuum of early and late brain disruption. Mitochondrial respiratory chain abnormalities, mainly affecting complexes I and IV, and deficiency of pyruvate dehydrogenase complex were detected in skeletal muscle and in liver. A normal functioning of the respiratory chain was found in the fibroblasts. Analysis of mtDNA from muscle, liver and blood revealed normal amounts of intact mtDNA without any of the known point mutations associated with MELAS, MERRF or Leigh syndromes. The early fetal disruption and necrotic changes in the brains of sibs indicate a specific genetically determined disorder which affects neuronal migration, a finding not previously associated with respiratory chain disorders. The present disorder may mimic antenatal congenital infectious encephalopathy because of the combined finding of microcephaly and destructive intracerebral calcification.

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Abbreviations

COX :

cytochromec oxidase

CS :

citrate synthase

PC :

pyruvate carboxylase

PDHc :

pyruvate dehydrogenase complex

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Author information

Authors and Affiliations

  1. Department of Paediatrics, Free University Hospital, De Boelelaan 1117, NL-1081 HV, Amsterdam, The Netherlands

    J. F. Samsom & C. Jakobs

  2. Division of Neuropathology, Free Univesity Hospital, Amsterdam, The Netherlands

    P. G. Barth

  3. Department of Obstetrics, Free University Hospital, Amsterdam, The Netherlands

    J. I. P. de Vries

  4. Department of Clinical Genetics, Free University Hospital, Amsterdam, The Netherlands

    F. H. Menko

  5. Department of Paediatrics, University Hospital Nijmegen, The Netherlands

    W. Ruitenbeek

  6. Department of Human Genetics, University Hospital Nijmegen, The Netherlands

    B. A. van Oost

Authors
  1. J. F. Samsom
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  2. C. Jakobs
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  3. P. G. Barth
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  4. J. I. P. de Vries
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  5. F. H. Menko
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  6. W. Ruitenbeek
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  7. B. A. van Oost
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Samsom, J.F., Jakobs, C., Barth, P.G. et al. Familial mitochondrial encephalopathy with fetal ultrasonographic ventriculomegaly and intracerebral calcifications. Eur J Pediatr 153, 510–516 (1994). https://doi.org/10.1007/BF01957007

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  • DOI: https://doi.org/10.1007/BF01957007

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