The biogenic amines, dopamine, serotonin, and noradrenaline, and their metabolites, were measured in selected brain regions obtained at postmortem from four patients ages 12-30 years with Rett syndrome and are reported from the Departments of Pediatrics, Psychiatry and Neurochemistry, Goteborg University, Goteborg, Sweden. The cause of death was sudden and unexpected in one, severe pneumonitis and pulmonary abscess in one, in association with an operation for scoliosis at 12 years of age in one, and was unrecorded in one. Three of the patients had epilepsy; two were receiving carbamazepine and one sodium valproate at the time of death. Compared to determinations in two adults who had drowned in ice cold water and one killed in a traffic accident, the two older patients with Rett syndrome showed a 50% or greater reduction in biogenic amines in the substantia nigra whereas the youngest patient showed normal or nearly normal levels of biogenic amines in the substantia nigra. The levels were normal in the caudate nucleus, putamen and globus pallidus. The oldest patients had rigidity and dystonic posturing at the time of death whereas the younger 12 year old child was motor disabled secondary to weakness and wasting. The biogenic amine data reflect the clinical patterns of the patients and parallel the neuropathologic finding of reduced melanin content in the neurons of the substantia nigra [1]. Dr. Percy is at the Department of Pediatrics, Baylor College of Medicine, Houston, TX.
COMMENT. Hagberg et al have previously reported a postmortem analysis of brain biogenic amines in an 11 year old Rett syndrome patient in whom the dopamine was markedly reduced in all regions of the brain except the cerebellum and parietal cortex (Ann Neuro 1983; 14:471). Motor dysfunction generally deteriorates steadily in Rett syndrome and parkinson-like features predominate during adolescence and early adulthood, suggesting a progressive involvement of the nigrostriatal system. Jellinger K, Percy AK et al. [2] have described the autopsy findings in nine girls with Rett syndrome, ages 4-17 years. All brains were smaller than normal, lipofuscin was deposited in neuronal cytoplasm, melanin was absent in substantia nigra, and indications of dopaminergic nigrostriatal dysfunction were suggested. The intensive search for a biological marker for Rett syndrome continues.