Metachromatic Leukodystrophy

SEPTEMBER IS LEUKODYSTROPHY MONTH

Metachromatic leukodystrophy is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme arylsulfatase A,  necessary for the normal hydrolysis of sulfatides (cerebroside 3-sulfate). Sulfatides are a component of the myelin. With metachromatic leukodystrophy, sulfatides accumulate within glial cells and neurons in the white matter of the brain, destroying normal myelin. It is diagnosed biochemically on the basis of an abnormally low level of arylsulfatase A in peripheral blood leukocytes and in the urine.   

There are three types of metachromatic leukodystrophy based on patient age at presentation: late infantile, juvenile, and adult. The most common type is late infantile metachromatic leukodystrophy.  Our patient presented as an adult. Adult metachromatic leukodystrophy can appear in adults of any age. The first symptoms are often changes in personality. Adult metachromatic leukodystrophy  is often misdiagnosed as other disorders such as schizophrenia or depression. As the disease progresses,  memory impairment, speech, and movement control slowly get worse . People with adult metachromatic leukodystrophy may sometimes live 10 to 30 years or more after onset.

MRI findings are symmetric, confluent high signal intensity on FLAIR / T2-weighted images in the periventricular white matter and centrum semiovale. A posterior predominance of white matter abnormalities has been noted.  Subcortical U fibers can be involved later in demyelination. Other sites of involvement were the genu and splenium of the corpus callosum, the posterior limbs of the internal capsule, the descending pyramidal tracts, the claustrum, and the cerebral white matter. Diffuse brain atrophy may result. No enhancement  is seen.

The only treatment that may affect the progression of metachromatic leukodystrophy  is a bone marrow or cord blood transplant. Transplant cells can make the arylsulfatase A . Recombinant human arylsulfatase A is being evaluated in Europe for enzyme replaement.

CheonJE, Kim IO, Hwang YS, et al. Leukodystrophy in children: a pictorial review of MR imaging features. RadioGraphics 2002; 22: 461–476.