New insights into the neuropathogenesis of molybdenum cofactor deficiency.
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.
Salman
Michael S
MS
Department of Neurology, Hospital for Sick Children, Toronto, ON, Canada.
Ackerley
Cameron
C
Senger
Christof
C
Becker
Laurence
L
D001344:Autopsy; D003067:Coenzymes; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008274:Magnesium / Q000032:analysis; D008297:Male; D008667:Metalloproteins / Q000172:deficiency*; D000090006:Molybdenum Cofactors; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology*; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000172:deficiency*; D011621:Pteridines; D013052:Spectrometry, X-Ray Emission; D013455:Sulfur / Q000032:analysis
D003067:Coenzymes; D008274:Magnesium; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D050862:Oxidoreductases Acting on Sulfur Group Donors; D011621:Pteridines; D013455:Sulfur; C022261:molybdopterin