Neurodegeneration in hereditary nucleotide repair disorders

Both xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are rar e autosomal disorders, have 3 genetic defect in the step of nucleotide repa ir, and involve various neurological abnormalities caused by progressive ne urodegeneration. We performed comprehensive neuropathological analysis of f ive cases of XPA and four casts of CS. The XPA cases showed widespread neur onal loss throughout the central nervous system, in sharp contrast to the c omparative preservation of neurons in the CS cases, who rather exhibited pa tchy demyelination in the cerebral and cerebellar white matter, and multifo cal calcium deposition in the basal ganglia and cerebral white matter, resp ectively. Exceptionally in the cerebellar cortex, neuronal loss was more se vere in CS than in XPA, Grumose or foamy spheroid bodies occurred in the gl obus pallidus and substantia nigra, and axonal torpedoes were increased in the cerebellar cortex in both disorders. Neither silver impregnation nor im munohistochemistry for ubiquitin or tau succeeded in visualizing neurofibri llary tangles, senile plaques or augmented ubiquitination in tither disorde r, and these finding did not support the involvement of facilitated aging i n the neurodegeneration in XPA or CS. (C) 1999 Elsevier Science B.V. All ri ghts reserved.