Ultrastructure of the optic nerve in Krabbe's leucodystrophy.

The leucodystrophies are a heterogeneous group of inherited neurological disorders all characterized by progressive symmetrical demyelination without any marked inflam-matory response, causing loss of motor, sensory, and intellectual functions with an eventual fatal outcome. Included in the group are metachromatic leucodystrophy (sulphatide lipidosis), Krabbe's globoid cell leucodystrophy, Canavan's spongy degeneration, Peli-zaeus-Merzbacher disease, and Alexander's disease. All the disorders are thought to be the result of defects in normal myelin metabolism, and it is probable that there is a genetically determined enzyme defect which is specific to each clinically and histopatho-logically distinguishable type. The exact biochemical nature of the defect has, however, been determined only in Krabbe's disease and in sulphatide lipidosis (Moser, I972). Krabbe's disease is a leucodystrophy of very early onset, the progressive global deterioration ofcerebral function commencing within a few weeks ofbirth (Krabbe, 19I6). Affected infants fail to thrive and become increasingly irritable with characteristic bouts of incon-solable crying. Tonic seizures and spastic quadriplegia develop and most affected children become deaf and also blind as the result of optic atrophy before they die, in a decerebrate state, in the second year of life, usually from the intervention of a severe respiratory infection. The demyelinating process is characteristically associated with the accumulation of epithelioid cells and of large multinucleated globoid cells in the degenerate white matter (Collier and Greenfield, 1924). The disease follows an autosomal recessive pattern of inheritance, and a deficiency of the enzyme galactocerebroside beta-galacto-sidase has been demonstrated recently, not only in the brain but also in the viscera, leuco-cytes, and serum ofpatients with Krabbe's disease (Suzuki and Suzuki, I970, 197I). Total glycolipids are reduced in the brain, typically with an increase in the ratio of cerebrosides to sulphatides, and there is also a low level of cerebroside sulphotransferase activity (Bachhawat, Austin, and Armstrong, I 967). The exact mechanism by which the inherited enzyme defect gives rise to the characteristic biochemical, neurological, and histopatho-logical manifestations of the disease is not yet fully understood. The reason for the relative decrease in cerebroside concentration in the brain, despite a defect in its catabolic pathway, is thought to be reduced synthesis of cerebroside by the oligodendrocytes which decrease in number early in the disease on account of the massive accumulation of globoid cells within the white matter (Suzuki and Suzuki, 1970). Sayre, and Hayles, I963) have demonstrated that globoid cells tend to have a perivascular distribution within the cerebral white …