Metachromatic Leukodystrophy Sulfatide Lipidosis

Metachromatic leukodystrophy or sulfatide lipidosis is an autosomal recessive disorder affecting chiefly infants, but juvenile and adult variants are also known. It is caused by deficiency of the lysosomal enzyme arylsulfa-tase A (ASA). The ASA gene is located on chromosome 22. ASA normally degrades the myelin sulfatides to cerebroside and inorganic sulfate (Table 9.6). A deficiency of the enzyme ASA results in the excessive accumulation of sulfatides in the myelin, rendering it chemically unstable and prone to disintegration. Grossly, the cerebral and cerebellar white matter is diffusely soft in early stages and firm and yellowish in chronic stages. The subcortical white matter usually is spared, except in longstanding cases, in which it also degenerates (Fig. 9.11). A general autopsy may show a fibrotic gall bladder. Histologically, the myelin breakdown products contain large amounts of sulfatides which, in frozen sections, stain metachromatically brown with acidified cresyl violet, giving the name to the disease. Sulfatides may accumulate in the neurons of the cerebral gray structures, brainstem, spinal cord, and retina. Metachro-matic myelin globules are demonstrated in the biopsied sural nerve. Sulfatides are also deposited in the tubular epithelium of the kidneys and mucosa of the gall bladder (see Fig. 9.11). Increased levels of sulfatides in the urine and the presence of metachromatic granules in the sediment are easily demonstrated.

0 0

Post a comment