Symptoms and signs
Some specific symptoms vary from one type of leukodystrophy to the next, but the vast majority of symptoms are shared as the causes for the disease generally have the same effects. Symptoms are dependent on the age of onset, which is predominantly in infancy and early childhood, although the exact time of onset may be difficult to determine. Hyperirritability and hypersensitivity to the environment are common, as well as some tell-tale physical signs including muscle rigidity and a backwards-bent head. Botox therapy is often used to treat patients with spasticity. Juvenile and adult onsets display similar symptoms including a decrease or loss in hearing and vision. While children do experience optic and auditory degeneration, the course of the disease is usually too rapid, causing death relatively quickly, whereas adults may live with these conditions for many years. In children, spastic activity often precedes progressive ataxia and rapid cognitive deterioration which has been described as mental retardation. Epilepsy is commonplace for patients of all ages. More progressed patients show weakness in deglutition, leading to spastic coughing fits due to inhaled saliva. Classic symptomatic progression of juvenile X-linked adrenoleukodystrophy is shown in the 1992 film, Lorenzos Oil.Course and timetable are dependent on the age of onset with infants showing a lifespan of 2–8 years, juveniles 2–10 years and adults typically 10+ years. Adults typically see an extended period of stability followed by a decline to a vegetative state and death.
In other words, for an individual to inherit the leukodystrophy phenotype, he or she must carry two of the recessive, mutant alleles. Krabbe disease and metachromatic leukodystrophy (MLD) are two of such type. MLD is found on human chromosome 22 at position q13.31. Another type of inherited leukodystrophy is X-linked adrenoleukodystrophy (X-ALD). As its name implies, this type of leukodystrophy is the result of a mutation found on the X-chromosome. It is also carried in a recessive pattern. The X chromosome is a sex chromosome, and since women have two "chances" of acquiring a normal X chromosome (one maternal, one paternal), and males only one (one maternal), this disease is more likely to be seen in men than in women. The mutation resulting in adult-onset leukodystrophy is mapped at 5q23. Pathophysiology
Although there are nearly forty different types of leukodystrophies, many are lacking in formal and comprehensive research. Most of the research so far has been done on five types: (1) metachromatic leukodystrophy (MLD), (2) Krabbe disease, (3) X-Linked adrenoleukodystrophy (ALD), (4) Canavan disease, and (5) Alexander disease. Each type of leukodystrophy has a unique pathophysiology, but all five of these in some way affect a subset of glial cells, therefore disrupting myelin production and maintenance, and usually involve a mutation involving genes that code for enzymes necessary for the catabolism of very long chain fatty acids (VLCFAs) that are toxic to the myelin-producing cells of the central nervous system.