What Is Krabbe Disease? Krabbe disease, also known as globoid cell leukodystrophy, is an inherited disease of the nervous system. Leukodystrophies are a group of diseases affecting the myelin sheath, a fatty covering that insulates and protects nerve cells. Individuals with Krabbe disease lack an enzyme called galactocerebrosidase. This enzyme deficiency is caused by mutations in the GALC gene and results in the build-up of toxic substances in the cells that produce the myelin sheath. Without this protective covering, brain cells die and nerves in the body cannot function properly. There are two forms of the disease: infantile and late-onset. Infantile Form The infantile form, which affects 85 to 90% of individuals with Krabbe disease, appears in the first few months of life and causes irritability, muscle weakness, unexplained fever, deafness, blindness, seizures, and slowed mental and physical development. Usually, death occurs by the age of two, often due to respiratory failure. Late-Onset Form The late-onset form of Krabbe disease, which affects 10 to 15% of individuals with the disease, can appear at any time between the ages of six months and 50 years. These individuals slowly develop vision loss, difficulty walking, rigid muscles, and mental impairment. Symptoms among those with late-onset Krabbe disease are highly variable. The disease is often fatal 2 to 7 years after symptoms begin. How Common Is Krabbe Disease? The incidence of Krabbe disease is approximately 1 in 100,000 births in the United States. The condition has a higher incidence among several Druze and Muslim communities in and around Israel. How Is Krabbe Disease Treated? Treatment for Krabbe disease will depend on which form of the disease an individual has. Treatment options for both forms are listed below. Infantile Form For infants with this form of Krabbe disease who have not yet started showing symptoms, treatment with umbilical-cord blood stem cells has shown promise in enabling normal or near-normal lives. This procedure can take place within weeks of birth. In many cases neural deterioration is slowed following the procedure and symptoms seem less severe. Bone-marrow stem cells may be used in place of umbilical-cord blood stem cells, but cord blood stem cells are less particular and do not require the donor to be a perfect match. With cord blood stem cells, there is also less risk of immune-system complications. Infants who have already started showing symptoms of the disease do not seem to benefit from this treatment. For them, the only treatment is to address symptoms as they arise. Late-Onset Form Some individuals with late-onset Krabbe disease have benefited from treatment with umbilical-cord stem cells, although this treatment has been most successful in pre-symptomatic patients with the infantile form of the disease. In cases where the treatment has been successful, neural deterioration is slowed and symptoms are less severe. Just as with the infantile form of the disease, bone-marrow stem cells may be used in place of umbilical-cord blood stem cells for the late-onset form, but cord blood stem cells are less particular and do not require the donor to be a perfect match. With cord blood stem cells, there is also less risk of immune-system complications. For individuals who are not candidates for the procedure, the only treatment is to address symptoms as they arise. What Is the Prognosis for an Individual with Krabbe Disease? The infantile form of Krabbe disease is usually fatal before the age of two. Those infants who receive cord blood stem cells before the appearance of symptoms have longer lifespans. While their course is milder compared to untreated infants, these children still generally develop symptoms, including rigid muscles and difficulties with language and motor skills. Those with late-onset Krabbe disease typically live between two and seven years after the onset of symptoms. The exact symptoms and rate of neurological deterioration varies greatly from among individuals, even among those in the same family who have the same genetic mutations. Other names forKrabbe disease GALC deficiency Galactocerebrosidase deficiency Galactosylceramidase deficiency Galactosylceramide lipidosis Globoid cell leukodystrophy Globoid cell leukoencephalopathy References Adang et al., 2017, Mol Genet Metab, 122(1-2):18-32, http://dx.doi.org/10.1016/j.ymgme.2017.08.006 Escolar et al., 2016, J Neurosci Res, 94(11):1118-25, PMID: 27638597 Graziano et al., 2015, Gene, 555(1):2-13, PMID: 25260228 OMIM: Online Mendelian Inheritance in Man, OMIM [245200], 2016, http://www.omim.org/entry/245200 Wenger, 2011, https://www.ncbi.nlm.nih.gov/books/NBK1238/