What is Krabbe Disease?
Krabbe disease (pronounced krab A), is a rare genetic disorder, also known as globoid cell leukodystrophyAnother name for Krabbe disease, a rare and usually fatal disorder of the nervous system.. Krabbe disease is described as a severe neurological condition that results from the loss of the protective covering (myelinMyelin is an essential material your body uses to surround and protect nerve fibers. 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 leukodystrophyThe leukodystrophies comprise a group of progressive, genetic disorders mainly affecting the central nervous system (CNS). Most leukodystophies result from a disruption of the growth of the myelin shand 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 enzymeA protein needed by the body to break down certain substances by causing a biochemical reaction within the cells. In Krabbe disease, galactocerebrosidase is the deficient enzyme. Words that end in 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 galactocerebrosidaseA specific enzyme that receives its instructions from the GALC gene. When the GALC gene isn’t working properly, the enzyme, galactocerebrosidase, is unable to break down certain fats called galactol More (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 cellsThe abnormal cells found in the brain of patients with Krabbe disease have a characteristic pathology known as globoids cells, which are large cells usually with more than one nucleus. and loss of myelin (demyelinationA process whereby the body breaks down the protective coating surrounding nerves.) 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 systemThe central nervous system (CNS) is made up of the brain and the spinal cord. (CNS)(e.g., brain and spinal cord) and the peripheral nervous systemThe nervous system of the body is made up of the Central Nervous System (CNS) and the Peripheral Nervous System (PNS)., 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 inheritedThe way genes are passed down from one generation to the next. There are many different types of inheritance patterns. Krabbe disease is inherited in an autosomal recessive pattern of inheritance. 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 mutationsThis is an older word used to describe a change in a specific gene leading to disease. As not all mutations are bad, the word mutation has been replaced with the term “pathogenic variant” that d are responsible for Krabbe disease in the Druze and Moslem Arab populations in Israel. Hum Genet. 1996; 97:304-8.