Acta Neuropathologica

, Volume 97, Issue 5, pp 469–480

Increased density of oligodendrocytes in childhood ataxia with diffuse central hypomyelination (CACH) syndrome: neuropathological and biochemical study of two cases

Authors

  • D. Rodriguez
    • Service de Neuropédiatrie, Hôpital Saint Vincent de Paul, AP-HP, 74–82 avenue Denfert-Rochereau, F-75674 Paris Cedex 14, France e-mail: drodrig@infobiogen.fr, Fax: +33-1-40-48-83-56
  • A. Gelot
    • Service d’Histo-Embryologie, Cytogénétique, Anatomopathologie, Hôpital Saint Vincent de Paul, AP-HP, Paris, France
  • B. della Gaspera
    • Laboratoire de Neurogénétique Moléculaire, CNRS URA 1488, Université de Paris VI, Paris, France
  • O. Robain
    • INSERM U29, Hôpital Port-Royal, Paris, France
  • G. Ponsot
    • Service de Neuropédiatrie, Hôpital Saint Vincent de Paul, AP-HP, 74–82 avenue Denfert-Rochereau, F-75674 Paris Cedex 14, France e-mail: drodrig@infobiogen.fr, Fax: +33-1-40-48-83-56
  • L. L. Sarliève
    • Laboratoire de Neurobiologie Moléculaire des Interactions cellulaires, CNRS UPR 416, Université Louis Pasteur, Strasbourg, France
  • S. Ghandour
    • Laboratoire de Neurobiologie Moléculaire des Interactions cellulaires, CNRS UPR 416, Université Louis Pasteur, Strasbourg, France
  • A. Pompidou
    • Service d’Histo-Embryologie, Cytogénétique, Anatomopathologie, Hôpital Saint Vincent de Paul, AP-HP, Paris, France
  • A. Dautigny
    • Laboratoire de Neurogénétique Moléculaire, CNRS URA 1488, Université de Paris VI, Paris, France
  • P. Aubourg
    • Service de Neuropédiatrie, Hôpital Saint Vincent de Paul, AP-HP, 74–82 avenue Denfert-Rochereau, F-75674 Paris Cedex 14, France e-mail: drodrig@infobiogen.fr, Fax: +33-1-40-48-83-56
  • D. Pham-Dinh
    • Laboratoire de Neurogénétique Moléculaire, CNRS URA 1488, Université de Paris VI, Paris, France
Regular paper

DOI: 10.1007/s004010051016

Cite this article as:
Rodriguez, D., Gelot, A., della Gaspera, B. et al. Acta Neuropathol (1999) 97: 469. doi:10.1007/s004010051016

Abstract

We report neuropathological, biochemical and molecular studies on two patients with childhood ataxia with diffuse central nervous system hypomyelination (CACH) syndrome, a leukodystrophy recently defined according to clinical and radiological criteria. Both had severe cavitating orthochromatic leukodystrophy without atrophy, predominating in hemispheric white matter, whereas U-fibers, internal capsule, corpus callosum, anterior commissure and cerebellar white matter were relatively spared. The severity of white matter lesions contrasted with the rarity of myelin breakdown products and astroglial and microglial reactions. In the white matter, there was an increase in a homogeneous cell population with the morphological features of oligodendrocytes, in many instances presenting an abundant cytoplasm like myelination glia. These cells were negative for glial fibrillary acidic protein and antibodies PGM1 and MIB1. Some were positive for myelin basic protein, proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein, but the majority were positive for human 2′-3′ cyclic nucleotide 3′ phosphodiesterase and all were positive for carbonic anhydrase II, confirming that they are oligodendrocytes. Myelin protein and lipid content were reduced. The PLP gene, analyzed in one case, was not mutated or duplicated. The increased number of oligodendrocytes without mitotic activity suggests an intrinsic oligodendroglial defect or an abnormal interaction with axons or other glial cells. This neuropathological study supports the notion that CACH syndrome constitutes a specific entity.

Key words LeukodystrophyOligodendrocyteMyelinOrthochromaticCACH syndrome

Copyright information

© Springer-Verlag Berlin Heidelberg 1999