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New Insights into the Neuropathogenesis of Molybdenum Cofactor Deficiency

  • Michael S. Salman (a1), Cameron Ackerley (a2), Christof Senger (a2) and Laurence Becker (a2) (a3)

Abstract

Background:

Molybdenum cofactor deficiency (MOCOD) is a rare, progressive neurodegenerative disorder caused by sulphite oxidase enzyme deficiency. The neuropathological findings are consistent with a toxic insult to the brain that causes severe neuronal loss, reactive astrogliosis and spongiosis. The mechanisms responsible for these changes are unknown.

Methods:

The case is a male infant with MOCOD who died at nine months of age from pneumonia. At autopsy, a complete neuropathological examination was performed including conventional immunohistochemical staining. In addition, brain sections were stained cytochemically with shikata and orcein which stain for disulphide bonds. The elemental composition of cortical cells was then analyzed in the scanning electron microscope using backscatter electron imaging and energy dispersive X-ray spectrometry.

Results:

Neurons demonstrated cytoplasmic staining with shikata and orcein cytochemically when compared to control sections. Energy dispersive X-ray spectrometry analysis of these neurons confirmed the presence of excess sulphur and unexpectedly revealed excess magnesium accumulation. None of these findings was found in an age-matched control.

Conclusions:

In MOCOD we found abnormal accumulation of sulphur and magnesium in neurons. It is postulated that sulphur-containing compound(s) that are formed as a result of MOCOD cause excitotoxic neuronal injury in the presence of excess magnesium.

RÉSUMÉ: Introduction:

La déficience en cofacteur à molybdène (DCOMO) est une maladie neurodégénérative progressive rare causée par une déficience en sulphite oxydase. Les observations neuropathologiques sont compatibles avec une lésion toxique du cerveau qui cause une perte neuronale sévère, une astrogliose et une spongiose réactionnelles. Les mécanismes responsables de ces changements sont inconnus.

Observation:

Il s'agit d'un enfant mâle atteint de DCOMO qui est décédé à l'âge de neuf mois de pneumonie. Àl'autopsie, un examen neuropathologique complet a été effectué, ainsi que des études conventionnelles de coloration immunohistochimiques et des colorations cytochimiques au shikata et à l'orcéine qui colorent les ponts disulphures. La composition élémentaire des cellules corticales a ensuite été analysée au microscope électronique à balayage utilisant la scintigraphie électronique radiodiffusée et la spectrométrie de rayons X induits par particules chargées.

Résultats:

Contrairement aux sections contrôles, les neurones présentaient une coloration cytoplasmique au shikata et à l'orcéine. L'analyse spectrométrique de ces neurones a confirmé la présence d'un excès de soufre et a montré la présence insoupçonnée d'un excès de magnésium. Aucune de ces observations n'a été retrouvée chez des contrôles appariés pour l'âge.

Conclusions:

Dans le DCOMO, nous avons observé une accumulation anormale de soufre et de magnésium dans les neurones. Nous postulons que le(s) composé(s) soufré(s) qui sont formés dans la DCOMO causent une lésion neuronale excitotoxique en présence d'un excès de magnésium.

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References

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New Insights into the Neuropathogenesis of Molybdenum Cofactor Deficiency

  • Michael S. Salman (a1), Cameron Ackerley (a2), Christof Senger (a2) and Laurence Becker (a2) (a3)

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