The leukodystrophies are diseases that affect the white matter of the CNS (Table 31–1). These diseases can begin in infancy, childhood, or adulthood. Infantile-onset leukodystrophies are generally characterized by initial hypotonia followed by spasticity and mental retardation. Seizures may also occur. In childhood-onset leukodystrophies, there is typically developmental and motor regression. Adult-onset leukodystrophies are characterized by dementia, psychiatric symptoms, and development of spasticity.
TABLE 31–1Clinical and Laboratory Features of the Leukodystrophies. ||Download (.pdf) TABLE 31–1 Clinical and Laboratory Features of the Leukodystrophies.
| || || ||Neuroimaging || || || || |
| || Age of Onset ||Unique Clinical Features ||White Matter Changes ||U Fibers || Gene Mutation || Inheritance ||Diagnosis || Other |
|Adrenoleukodystrophy ||Childhood (most commonly 4–8 years old) or adulthood || |
Visual and/or behavioral problems in children
Adrenomyelo-neuropathy can occur in adults
|Posterior predominance ||Spared ||ABCD1 ||XL ||Plasma very long chain fatty acids || |
Bone marrow transplant
|Alexander disease ||Any age || |
|Frontal predominance ||Involved ||GFAP ||Sporadic or AD ||Genetic testing ||Pathology: Rosenthal’s fibers |
|Canavan disease ||Infancy ||Macrocephaly ||Diffuse ||Involved ||Aspartoacylase ||AR || |
Decreased aspartoacylase activity in skin fibroblasts
|Increased NAA peak on MR-spectroscopy |
|Krabbe disease ||Any age (but most commonly infancy) || |
|Posterior predominance ||Spared ||Galactocerebrosidase ||AR || |
Decreased galactocerebrosidase activity in skin fibroblasts
Globoid cells on pathology
Treatment with bone marrow transplant
|Metachromatic leukodystrophy ||Any age ||Peripheral neuropathy ||Frontal predominance ||Spared ||Arylsulfatase A ||AR || |
Decreased arylsulfatase A activity in skin fibroblasts
|Treatment with bone marrow transplant |
|Pelizaeus-Merzbacher disease || |
Infancy or childhood
|Eye movement abnormalities ||Diffuse ||Spared ||PLP1 ||XL ||Genetic testing ||Pathology: tigroid appearance of white matter |
|Vanishing white matter disease ||Any age || |
Ataxia and/or spasticity
Ovarian failure may be seen in affected women
|White matter hypointense (“vanished”) rather than hyperintense as in other leukodystrophies ||Involved ||eIF2B ||AR ||Genetic testing || |
Many individual leukodystrophies have particular clinical hallmarks (e.g., neuropathy in Krabbe disease and metachromatic leukodystrophy) and particular distributions of white matter changes on MRI (involving or sparing the juxtacortical U fibers; frontal vs posterior predominant). Adrenoleukodystrophy, Krabbe disease, and metachromatic leukodystrophy can be treated with bone marrow transplantation, but the other leukodystrophies are treated supportively. Distinctive clinical and imaging features (beyond core features listed above) and genetics of the leukodystrophies are listed in Table 31–1.
Adrenomyeloneuropathy is a subtype of adrenoleukodystrophy that presents in adulthood with myelopathy, neuropathy, and adrenal insufficiency (the brain can be involved, but often is not, unlike the other leukodystrophies). Therefore, adrenomyeloneuropathy should be considered in the differential diagnosis for combined myelopathy and neuropathy (myeloneuropathy), as can also be seen with vitamin B12 deficiency and copper deficiency. As with adrenoleukodystrophy, inheritance of adrenomyeloneuropathy is X-linked, and diagnosis is made by elevated serum very long chain fatty acids (VLCFAs) and genetic testing. Treatment for the condition is limited to the treatment of the adrenal ...