Metachromatic Brain

Metachromatic leukodystrophy AR Aryl sulfatase A Accumulation of sulfatide in brain see text 1,2, Ch. 40... 

Iversen SD 5-HT and anxiety. Neuropharmacology 23 156-164, 1984 Iwamori M, Moser HW, Kishimoto Y Steroid sulfatase in brain comparison of sulfohydrolase activities for various steroid sulfates in normal and pathological brains, including various forms of metachromatic leukodystrophy. J Neurochem 27 1389-1395, 1976... 

The monocarboxylic acid connected in amide conjugation to the amino group of the sphingosine residue proved to consist mainly of the Ci8-fatty acid. The gangliosides of Niemann-Pick disease and metachromatic leucodystrophy differ from those of normal, infant and adult brains, in that C24-acids were not detected. The development of new ultramicro methods led to the exact (differential) determination of the constituents of these gangliosides215 of disease. 

Isol. from mammalian brain and spinal cord. Accumulates abnormally in patients with metachromatic leukodystrophy. Major acidic glycosphingolipid responsible for negative charge on nerve cell membranes. 

In metachromatic leukodystrophy, the brain is often heavier than normal. The leukodystrophy is diffuse, as in the globoid type. Demyelinization, astrocytosis, and histiocytosis are found in the areas of leukodystrophy. Metachromatic globules are dispersed in the white matter and within histiocytes. Groups of neurons containing metachromatic lipids are also often found (see... 

It has been shown that the lipid composition of the brain of mentally diseased adults is often similar to that of normal infants much more sulphatide is found in cases of metachromatic leucodystrophy [69, 72, 177] large amounts of one ganglioside appear in Tay-Sachs disease [96, 177] and a greatly increased sphingomyelin content of the brain is found with the Niemann-Pick disease [164, 177]. The cerebroside sulphate esters of the brain of normal persons and of those suffering from metachromatic leucodystrophy have been isolated by TLC and shown to be identical [69]. 

Rouser, G., C. Galli, and G. Kritchevsky Lipid class composition of normal human brain and variations in metachromatic leucodystrophy, Tay-Sachs, Niemann-Pick, chronic Gaucher s and Alzheimer s disease. J. Amer. Oil Chemists Soc. 42, 404 (1965). 

In 1950, Brain and Greenfield noted metachromatic deposits in cerebral white matter and in the epithelium of renal tubuli, and distention of ganghon cells and pointed out the homogeneity of reported cases. Hirsch and Peiffer (1955) made a systematic histochemical study of the myelin degradation products in leucodystrophy, examining the cases of Scholz (1925), van Bogaert and Scholz (1932), Scholz (1933), van Bogaert and Bertrand (1933) and Wicke... 

Comparative histochemical and chemical analyses have shown that the accumulated metachromatic material is identical with the sulfatide which has been isolated from brain and other organs of ML (Jatzkewitz 1958, 1960 b Austin 1958, 1959 a, b, 1960 Hagberg et al. 1960) (see below). 

Table 4. Long-chain fatty acids of sulfatide, cerehroside and sphingomyelin of brain white matter in metachromatic leucodystrophy...

Biopsies from peripheral nerves (sciatic nerve) or from brain tissue may establish the diagnosis when a large amount of metachromatic material is found. The occurrence of small amounts is non-specific and may be seen in other demyelinating diseases (Einarson and Neel 1938 Jervis 1960). 

Recent studies in metachromatic and globoid body forms of diffuse sclerosis. In Brain lipids and lipoproteins, and the leucodystrophies. Eds J. Folch-Pi and H. J. Bauer. Amsterdam-London-New York Elsevier Publishing Co. 1963 a, p. 120. 

D. Armstrong, and L. Shearer Metachromatic form of diffuse cerebral sclerosis. V. The nature and significance of low sulfatase activity A controlled study of brain, liver and kidneys in four patients with metachromatic leukodystrophy (MLD). Arch. Neurol. (Chic.) 13, 593 (1965 a). 

Brain, W., and J. G. Greenfield Late infantile metachromatic leucoencephalopathy with primary degeneration of the interfascicular oligodendroglia. Brain 73, 291 (1950). 

Mossakowski, M., G. Mathieson, and N. Cumings On the relationship of metachromatic leucodystrophy and amaurotic idiocy. Brain 84, 585 (1961). 

Norman, R. M. Diffuse progressive metachromatic leucoencephalopathy. A form of Schilder s disease related to the lipoidoses. Brain 70, 234 (1947). 

Sulfatide, which is particularly abundant in the white matter of the brain, is degraded by arylsulfatase A. This enzyme needs the assistance of a protein cofactor, SAP-B [18], Deficiency of this enzyme leads to metachromatic leukodystrophy, a disease which is due to sulfatide accumulation in various organs and which primarily affects the white matter of the brain [39]. Also the inherited deficiency of SAP-B leads to a lysosomal storage disease which resembles metachromatic leukodystrophy. However unlike typical metachromatic leukodystrophy not only sulfatide but also additional glycolipids, e.g. globotriaosylceramide, accumulate due to defects in several points of the pathway of GSL degradation [20]. 

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