NEUROPATHOLOGY OF RETT-SYNDROME - CASE-REPORT WITH NEURONAL AND MITOCHONDRIAL ABNORMALITIES IN THE BRAIN

Neuronal changes in the brain of a Rett syndrome patient were examined in a frontal lobe biopsy performed at age 3 years and in the postmort em brain at age 15 years. In the brain biopsy, frontal cortex containe d numerous scattered pyramidal neurons with cytoplasmic vacuolation an d increased cytoplasmic density, with no neuronophagia or inflammation detected; electron microscopy showed these neurons to have large, luc ent-appearing mitochondria, very abundant ribosomal content, and some lipofuscin granules. Postmortem brain 12 years later showed scattered neurons in frontal cortex, substantia nigra, and cerebellar folia, wit h increased electron density of the cytoplasm, stacks of ribosomal end oplasmic reticulum, and large amounts of disorganized membranous mater ial, including autophagic-type organelles. Mitochondria of these neuro ns contained electron-dense, finely granular matrix inclusions; in the substantia nigra, some spherical mitochondrial inclusions completely filled the matrix space. Golgi preparations of (autopsy) frontal corte x and cerebellar folia showed truncation and thickening of dendrites a nd a degenerate appearance of cortical pyramidal neurons, similar to c hanges found in aged brain. Synaptophysin immunohistochemistry indicat ed that the density of synapses was not greatly altered compared to co ntrols in frontal cortex and cerebellum. The patient also had a second genetic defect, severe combined immunodeficiency with thymic aplasia, which may be X-Linked.