Interest in disorders of the white matter of the CNS started in the 19th century. For many decades, research in that field was dominated by pathology. Examples of the diseases defined on the basis of pathological findings include in chronological order: multiple sclerosis, Pelizaeus–Merzbacher disease, Schilder diffuse sclerosis, globoid cell leukodystrophy, metachromatic leukodystrophy, and Alexander disease. Halfway through the 20th century, after the identification of the biochemical basis of many white-matter disorders, diagnostics based on morphology were replaced by diagnostics governed by biochemistry. The general diagnostic approach became one of broad biochemical screening of body fluids, followed by more specific biochemical tests leading to a specific biochemical diagnosis.