Epidemiology
Currently, no research has shown a higher prevalence of most leukodystrophy types in any one place around the world. There is, however, a higher prevalence of the Canavan disease in the Jewish population. 1 in 40 individuals of Ashkenazi Jewish descent are carriers of Canavan disease. This estimates to roughly 2.5%. Additionally, due to an autosomal recessive inheritance patterns, there is no significant difference found between affected males and affected females for most types of leukodystrophy including, but not limited to, metachromatic leukodystrophy, Krabbe disease, Canavan disease, and Alexander disease. The one exception to this is any type of leukodystrophy carried on a sex chromosome, such as X-linked adrenoleukodystrophy, which is carried on the X-chromosome. Because of the inheritance pattern of X-linked diseases, males are more often affected by this type of leukodystrophy, although female carriers are often symptomatic, though not as severely so as males. Research
The National Institute of Neurological Disorders and Stroke (NINDS, under the U.S. National Institutes of Health) supports research on genetic disorders, including the leukodystrophies. NINDS also supports researchers who are working with the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN) which promotes advances in the diagnosis and treatment of leukodystrophies.The European Leukodystrophy Association also supports research into leukodystrophy. As of 2020, more than 387 research projects have been funded. Each year, ELA invites the international scientific community to submit research projects in the field of genetic leukodystrophies, the cerebral white matter in premature infants, and of myelin repair.
The GALC gene, found on chromosome 14 at position 31 (14q31), codes for the enzyme beta-galactocerebrosidase (GALC). GALC is a lysosomal enzyme responsible for the catabolism of galactolipids, especially psychosine, that are heavily distributed throughout the brain. A deficiency in GALC thus causes a buildup of these fatty acids known as globoid macrophages that destroy oligodendrocytes, thereby inhibiting myelin formation.Because of the presence of globoid cells clustered near white matter, Krabbe disease often goes by the name globoid cell leukodystrophy. Furthermore, new research has shown that Krabbe disease and globoid cell leukodystrophy may be distinct disease entities due to the secretion of inflammatory mediators by natural killer cells in some cases. This research has shown that Natural Killer cells have receptors (TDAG8) for certain glycosphingolipids that build up in an individual with leukodystrophy, again due to insufficient GALC levels, and when bound, target the Natural Killer cells for destruction thereby preventing their cytotoxic effects. These sphingolipids have been identified as galactosyl sphingosine and glycosyl sphingosine and are not present in unaffected individuals. Canavan disease
Canavan disease is a lesser-studied type of leukodystrophy that, like MLD and Krabbe disease, is also passed on in an autosomal recessive inheritance pattern. It is due to a mutation in the ASPA gene that encodes aspartoacylase, an enzyme needed to metabolize N-acetyl-L-aspartate (NAA). The mutation causes a deficiency of aspartoacyclase. NAA is involved in the formation of lipids, and if it is not broken down by aspartoacylase, excess levels of it build up causing demyelination.