Where has all the white matter gone?

The clinical description of genetically inherited white matter diseases began more than 100 years ago with the pathologic description of Pelizaeus–Merzbacher disease; it continued during the early years of the 20th century with such disorders as metachromatic leukodystrophy and Krabbe disease. Understanding the biochemical basis of some of the leukodystrophies began when the stored substrates and the enzymatic defects were identified. However, many diseases that affected white matter remained poorly characterized with unknown biochemical and molecular defects. The term leukodystrophy became too narrow and was broadened to the concept of leukoencephalopathy because many of these disorders consisted of a failure in myelination or hypomyelination rather than a loss of previously acquired myelin. A series of technical advances occurred in MRI technology and molecular genetics that allowed for the identification of new forms of leukoencephalopathies in the past several years, which were not limited to childhood onset but also included adult-onset white matter diseases.1

MRI markedly increased the awareness of white matter abnormalities, including disorders resulting in hypomyelination in addition to the previously described leukodystrophies. It took the marriage of …