Krabbe Disease (globoid cell leukodystrophy)
Krabbe disease, also known as globoid cell leukodystrophy, is a rare, inherited, autosomal recessive disorder that affects the nervous system. It occurs in up to 1 in 100,000 people in the United States. People affected by Krabbe disease have a deficiency of the galactocerebrosidase (GALC) enzyme, which helps break down toxic fats, including psychosine and galactosylceramide, in the nervous system. This enzyme deficiency is due to disease-causing variants, or mutations, in the GALC gene.
Accumulation of psychosine and galactosylceramide is toxic to the nervous system, with excessive psychosine thought to lead to destruction of the myelin-forming cells throughout the nervous system. Myelin is a fatty substance that insulates nerve fibers and enables the efficient transmission of nerve signals from the brain to the rest of the body. The destruction of myelin leads to the signs and symptoms of Krabbe disease.
Krabbe disease is diagnosed via newborn screening in certain states in the US. Performed during the first few days of life, newborn screening for Krabbe disease measures GALC enzyme levels. Babies with low GALC enzyme levels may be further tested for diagnosis or monitoring.
In early infantile Krabbe disease, the most severe and rapidly progressive form of the disease, developmental delays are apparent before the age of six months, with some signs of disease arising soon after birth. Signs and symptoms include feeding difficulties, excessive crying, loss of previously attained milestones, seizures, muscle spasms, blindness, deafness and loss of voluntary movement. Due to rapidly progressive disease, individuals with this form of disease typically do not survive beyond 2-3 years of age when untreated.
Krabbe disease does not have a cure. Treatment is mainly supportive and includes seizure medications, placement of feeding tubes, among other interventions. Early diagnosis enables early treatment, which may improve the course of disease. Hematopoietic stem cell transplant, also referred to as umbilical cord transplant or bone marrow transplant, is currently used in infants with Krabbe disease who are diagnosed before symptoms become apparent. In addition, there are emerging treatments, such as gene therapy, under development.