European Journal of Pediatrics

, Volume 153, Issue 7, pp 510–516

Familial mitochondrial encephalopathy with fetal ultrasonographic ventriculomegaly and intracerebral calcifications

  • J. F. Samsom
  • C. Jakobs
  • P. G. Barth
  • J. I. P. de Vries
  • F. H. Menko
  • W. Ruitenbeek
  • B. A. van Oost
Neuropediatrics Original Paper

DOI: 10.1007/BF01957007

Cite this article as:
Samsom, J.F., Jakobs, C., Barth, P.G. et al. Eur J Pediatr (1994) 153: 510. doi:10.1007/BF01957007

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.

Key words

Cerebral calcification Lactic acidosisRespiratory chain Mitochondrial encephalopathy Neuronal migration

Abbreviations

COX

cytochromec oxidase

CS

citrate synthase

PC

pyruvate carboxylase

PDHc

pyruvate dehydrogenase complex

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • J. F. Samsom
    • 1
  • C. Jakobs
    • 1
  • P. G. Barth
    • 2
  • J. I. P. de Vries
    • 3
  • F. H. Menko
    • 4
  • W. Ruitenbeek
    • 5
  • B. A. van Oost
    • 6
  1. 1.Department of PaediatricsFree University HospitalAmsterdamThe Netherlands
  2. 2.Division of NeuropathologyFree Univesity HospitalAmsterdamThe Netherlands
  3. 3.Department of ObstetricsFree University HospitalAmsterdamThe Netherlands
  4. 4.Department of Clinical GeneticsFree University HospitalAmsterdamThe Netherlands
  5. 5.Department of PaediatricsUniversity Hospital NijmegenThe Netherlands
  6. 6.Department of Human GeneticsUniversity Hospital NijmegenThe Netherlands