Metachromatic form of diffuse cerebral sclerosis

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Abstract
Cerebroside sulfuric acid esters (CSAE) and other lipids were measured in controlled series of human white matter and kidney. Statistically significant elevations of CSAE occurred only in metachromatic leukoencephalopathy (ML). Controls with even minimal disorders of myelin had lower than normal CSAE. The CSAE excess is an actual and not only an apparent one, as shown by the even greater increase in kidneys, where structure is relatively preserved. CSAE samples in ML are galactosphingo-sulfatides, strongly metachromatic, doubly refractile in polarized light, and pink with PAS. Their primary mechanism of metachromasia under conditions cited may be discretely related to dissociated sulfuric acid ester groups on sulf atlde macromolecules. In ML white matter, CSAE values are disproportionately elevated, compared to low values for other myelin lipids such as total cholesterol and cerebrosides. Lowering of other lipids correlates histochemically with the lack of myelin. A proportionately greater fall of cerebron-like cerebrosides than of cholesterol is a possibility raised and qualified in ML white matter. Cerebroside sulfuric acid esters are normal constituents of white matter, correlate with some of the intense metachromasia of myelin sheaths, and appear chromatographically in overlapping subtractions. Normal total CSAE values by methods cited were in a range of 45 to 53 mg/g. CSAE elevation in ML implies a defect in sulfatide turnover. General causes for such a turnover defect are noted, as are mechanisms by which it and its accompaniments might in turn interfere with proper synthesis, renewal, and removal of myelin. Quantitative increases of CSAE in both white matter and kidney suggest a working definition of ML biochemically as a sulfatide lipidosis, descriptively resembling the lipid storage diseases. Qualitatively, evidence presented thus far does not consistently separate CSAE in ML from controls. The one elevation of cholesterol esters in ML correlates histologically with phagocytes staining red with Sudan IV. In ML kidney, free cholesterol values slightly above control values may reflect some nonspecific lipid accumulation. Hexosamine increase is greatest in the ML white matter with the highest CSAE. Evidence is lacking for an increase in hexosamine in ML kidney here or for catecholamines in CSAE fractions. CSAE fractions from human ML white matter evolve in phagocytes in rat white matter through stages morphologically and histochemically similar to many of those in their human ML counterparts.