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
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.