Menkes' kinky hair disease: morphological and immunohistochemical comparison of two autopsied patients.

An autopsied patient with Menkes' kinky hair disease, who showed unusually long survival until the age of five years with typical neuropathological changes, was examined for distribution of neuronal depletion in the cerebral cortex, and the cerebellar changes were compared morphologically and immunohistochemically with those found in a younger patient (1 year 8 months old) reported previously. Neuronal loss in the cerebral cortex in the both cases, which was ill-defined and unassociated with gliosis, was preferentially distributed in the fifth and sixth layers, especially of the gyral bottom in almost all lobes in the older case. Therefore, this change was thought to be secondary to local ischemia caused by mechanical distortion at the stage of gyrus formation in addition to abnormal development. Ultrastructurally, a prominent increase of confronting cisternae (CC) complexes was found in the perikaryon and processes of Purkinje cells in both cases, and in the older patient CC complexes were arranged more densely and were transformed into concentric lamellar structures in the swollen dendrites. Immunohistochemically, the stainability of neurofilaments (NF, 200 kDa) in Purkinje cells, with or without somatic sprouts was faint or negative in the older patient compared with the marked or moderate positivity in the younger patient and age-matched controls. Empty baskets were absent and NF-positive axonal terminals and synaptophysin-positive granules on Purkinje cells were markedly decreased in both cases. These changes suggest that Purkinje cells degenerate progressively with time and that basket cells also are simultaneously involved.