What is Krabbe Disease?
Krabbe disease (pronounced krab A), is a rare genetic disorder, also known as globoid cell leukodystrophy. Krabbe disease is described as a severe neurological condition that results from the loss of the protective covering (myelin sheath) surrounding nerve cells. This protective myelin sheath is essential to insulate the nerves and ensure the rapid transmission of nerve signals throughout the body.
Krabbe disease is classified as both a leukodystrophy and a lysosomal storage disorder (LSD). Leukodystrophies results from degeneration of the white matter in the brain. The word leukodystrophy comes from the Greek roots- leuko meaning white, dys, standing for lack of, and troph meaning growth.
Lysosomal storage disorders result from an enzyme deficiency in the lysosome of the cell. The lysosome is also known as the recycling center of the cell and when there is a missing or deficient enzyme, like in Krabbe disease, the body is unable to breakdown certain substances and they accumulate. Think of leukodystrophies as a subcategory of the broader group of disorders known as lysosomal storage disorders.
Individuals affected by Krabbe disease do not make enough of a specific lysosomal enzyme called galactocerebrosidase (also called galactosylceramidase, or GALC). This enzyme deficiency is due to a genetic change in the galactosylceramidase (GALC) gene. As a result of the deficient enzyme, complex fatty substances are unable to be broken down and the storage causes the pathologic changes, most notably the formation of globoid cells and loss of myelin (demyelination) of the protective coating/covering surrounding the nerves. The myelin-covered nerve fibers are known as the white matter of the brain. Krabbe disease slowly damages the white matter, as well as the rest of the central nervous system (CNS)(e.g., brain and spinal cord) and the peripheral nervous system, which consists of the nerves outside the CNS.
Many aspects of the underlying pathology of Krabbe disease are largely unknown,1 and like many lysosomal storage disorders, there is wide range of disease symptoms impacting the age of onset and disease severity.
How Common is Krabbe Disease?
In the United States, Krabbe disease has been reported to affect approximately 1 in 100,000 individuals.2 Two isolated communities in Israel, one in the Druze community of Northern Israel and two Moslem Arab villages near Jerusalem, have reported a higher incidence of 6 cases per 1,000 people, with an increased carrier frequency of 1:6. 3
Krabbe disease is inherited in an autosomal recessive manner. For a child to be affected by an autosomal recessive disorder, two copies of the abnormal gene must be present; one copy of the abnormal gene inherited from the mother and one copy of the abnormal gene inherited from the father.
1 Wenger DA. Krabbe Disease. 2000 Jun 19 [Updated 2011 Mar 31]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2 Genetics Home Reference National Institutes of Health. Krabbe Disease Statistics. Accessed February 2018.
3 Rafi MA, Luzi P, Zlotogora J, Wenger DA. Two different mutations are responsible for Krabbe disease in the Druze and Moslem Arab populations in Israel. Hum Genet. 1996; 97:304–8.