Neurochemical alterations in Rett syndrome.

The Rett syndrome (RS) is a neurological disorder associated with severe mental deficiency and neurological manifestations of cortical and extrapyramidal dysfunction. The present report is (1) a postmortem brain study that compares the levels of choline acetyltransferase (ChAT) activity and the binding density of selected neurotransmitter receptors in four cases of RS and five normal controls of similar age and (2) a study of cerebrospinal fluid (CSF) concentrations of the endogenous tridecapeptide neurotensin in 12 RS patients and 8 controls of similar age. The level of ChAT activity was lower in many cortical and subcortical regions in the RS brains as compared to control levels. The number of NMDA, AMPA, mu opioid and neurotensin binding sites, as well as CSF concentrations of neurotensin, did not differ significantly from control levels. The results suggest that changes in specific neurotransmitter systems, particularly cholinergic neurons, in the thalamus, cerebellum and basal ganglia may underlie the progressive deterioration in motor and cognitive function characteristic of this disorder.