Preliminary brain autopsy findings in progredient Rett syndrome.

Postmortem human brain analyses have been performed to further evaluate pathogenetic aspects of the Rett syndrome. While there are no significant abnormalities with respect to amino acid concentrations in putamen, caudate nucleus, red nucleus and thalamus, the concentration of kynurenine is increased in putamen, caudate nucleus, gl. pallidus, raphe and amygdaloid n. In contrast, serotonin and its metabolite 5-hydroxyindole acetic acid are below normal levels. D2-receptor number is decreased and there is a significant drop in the concentration of the iron-binding protein ferritin. It can be concluded, that reduction of D2-receptors is due to loss of cholinergic and GABA-ergic cell bodies in the striatum or may be a response to iron deficiency. Low serotonergic and high kynurenergic activity may be of pathogenetic importance in the frequently observed cerebral seizures in Rett syndrome.