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Degenerative disorders without evidence of visceral storage include infantile neuroaxonal dystrophy (a neurofilament disorder diagnosed by finding spheroid bodies in nerve biopsy), Canavan disease (diagnosed by decreased N-acetylaspartase activity in fibroblasts and by DNA study), metachromatic leukodystrophy (diagnosed by decreased arylsulfatase activity in leukocytes and fibroblasts), leukodystrophy with cerebral calcifications (no confirmatory diagnostic test is available), Menkes disease (diagnosed by the combination of decreased serum copper, decreased serum ceruloplasmin, and an elevated ratio of dihydroxyphenylalanine to dihydroxyphenylglycol; or an increased uptake of labeled copper by cultured fibroblasts), Tay-Sachs disease (diagnosed by decreased hexosaminidase A activity in leukocytes and fibroblasts) and Krabbe's disease (diagnosed by decreased lysosomal galactocerebroside beta-galactosidase).
Infantile neuroaxonal dystrophy, Canavan disease, leukodystrophy with cerebral calcifications, Menkes disease and Krabbe's disease can be suspected but not excluded based on MRI findings. Infantile neuroaxonal dystrophy is associated with cerebellar atrophy with a hyperintense cortex on T2-weighted images. Canavan disease is associated with swollen gyri and increased signal on T2-weighted images of subcortical white matter (U-fibers), external and internal capsule, and thalamus. Leukodystrophy with cerebral calcification is associated with diffuse hyperintensity of cerebral white matter on T2-weighted images and areas of decreased signal intensity (calcification) close to the ventricles. Menkes disease is associated with cerebellar atrophy with subdural hygromas, infarctions demonstrated by MRI of the brain, and tortuous vessels demonstrated by MRA of the brain. Krabbe's disease is associated with prechiasmatic optic nerve enlargement.


Figure 114.1. MRI in Krabbe's disease [A] Transverse and [B] sagittal T1-weighted images showing engorged optic nerves.

Urine evaluation may be helpful in the diagnosis of degenerative central nervous system disorders with and without visceral storage. Sialic acid containing oligosaccharides and glycoprotein may be present in sialidosis. Free sialic acid may be present in infantile sialic acid storage disease. Urinary level of N-acetylaspartate is increased in Canavan disease. The urine of neonates with metachromatic leukodystrophy shows decreased arylsulfatase activity. Mucopolysaccharides may be elevated in GM1 gangliosidosis.
Blood tests are also helpful in the diagnosis of degenerative central nervous system disorders. Plasma sialic acid is increased in infantile sialic acid storage disease. High serum concentration of very-long-chain fatty acids (>22 carbons) occurs in Zellweger syndrome and neonatal adrenoleukodystrophy. Serum N-acetylaspartate is increased in Canavan disease. Copper and ceruloplasmin may be low, and the ratio of dihydroxyphenylalanine to dihydroxyphenylglycol is elevated in Menkes disease.


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