In the classification of white matter disorders, the first big divider is whether the disease is inherited or not. This difference has major implications for the tests to be performed, for risk of recurrence in the family, and for potential therapeutic strategies.
The causes of the acquired forms can be subdivided according to type of cause into infectious-inflammatory, noninfectious-inflammatory, toxic-metabolic, traumatic and hypoxic-ischemic.
Because of the multitude of genes and proteins involved in the different disorders, the classification of hereditary white matter disorders is complex. The most useful classification follows the biochemical pathway that is involved. First of all, one can define disorders that involve a specific organelle in the cell. Organelles have specific functions and diseases affecting these organelles share certain characteristics. The genetic defect may affect proteins in lysosomes, the cleaning stations of the cell. A defect in lysosomes leads to a failure of the cell to dispose of a certain type of "garbage" and consequently to storage of unwanted substances (storage disorders). Peroxisomes have several functions. An important one is the breakdown of fatty acids with a very long chain. Mitochondria are the powerhouses of the cell. Mitochondrial disorders affect in particular the tissues that have a high energy demand, such as the brain, muscle, and the heart. The remaining hereditary white matter disorders can be classified according to the biochemical pathway in which the abnormality is located, such as pathways of amino acid and organic acid metabolism, processes of DNA repair, metabolism of myelin proteins, and so on.