Lysosomal diseases metachromatic leukodystrophy

Other lysosomal storage disorders include G j gangliosidoses, G gangliosidoses, Gaucher disease, Niemann-Pick disease, Fabry disease, fucosidosis, Schindler disease, metachromatic leukodystrophy, Krabbe disease, multiple sulfatase deficiency, Farber disease, and Wolman disease. Table 28-1 illustrates the enzyme deficiencies found in some of these disorders. 

Familial demyelinative/dysmyelinative and axonal neuropathies may also be caused by impaired lysosomal lipid metabolism. Metachromatic leukodystrophy (sulfatide lipidosis) results from mutations of the arylsulfatase A gene, which encodes a lysosomal enzyme required for sulfatide turnover. Myelin is affected in both CNS and PNS, though dysfunction is restricted to the PNS in some patients, and the onset of symptoms can occur at any time between infancy and adulthood. Bone marrow transplantation can slow disease progression and improve nerve conduction velocities [57]. (See in Ch. 41.)... 

Metachromatic leukodystrophy is another lysosomal storage disorder caused by a deficiency of arylsulfatase A which leads to the accumulation of 3-0-sulfogalactosylceramide. The defect results in severe demyelination. The disease often takes a presentation of an under- and mis-diagnosed psychiatric affection long before neurological symptoms appear and MRI displays the anatomical lesions. MRI reveals a diffuse demyelination, bilateral and often symmetrical, initially limited to the periventricular areas. 

A group of inherited diseases in which there are deficiencies of specific lysosomal hydrolases. The diseases are characterized by the deposition of complex lipids. They include Gaucher s disease, Fabry s disease, Krabbe s disease, Tay-Sachs disease, generalized gangliosidosis, Niemann-Pick disease and metachromatic leukodystrophy. 

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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