A Japanese brother and sister, the progeny of healthy parents, were born with thickened, wrinkled skin and died between the age of 2 and 3 years with a progressive cerebral disease characterized by generalized mental and motor impairment. Postmortem neuropathological studies disclosed a remarkable leukodystrophy in which multiple axonal spheroids were the outstanding feature. Ultrastructurally, the spheroids contained granules resembling ceroid-lipofuscin bodies. Similar granules were found in degenerating oligodendrocytes and in Schwann cells. The skin showed hypercellular and sclerotic features, suggestive of a genodermatosis. This combined neurologic and dermatologic syndrome, which, to our knowledge, has not hitherto been recognized, may well result from a genetically determined metabolic disorder, the nature of which still remains undisclosed.