Chapter 30 – Krabbe Disease: Globoid Cell Leukodystrophy

Krabbe disease or globoid cell leukodystrophy (GLD) is an autosomal recessive disorder of myelination caused by galactocerebrosidase (GALC) deficiency. This enzyme is essential for the lysosomal degradation of several important galactolipids, including galactosylceramide and psychosine. Most human patients present before 6 months of age but older patients are also recognized. The diagnosis can be made by measuring very low GALC activity in any easily obtainable tissue. Newborn screening has been initiated in an attempt to identify individuals who may develop the disease before symptoms appear. Treatment is limited to hematopoietic stem cell transplantation in presymptomatic infants and mildly affected late-onset patients. The GALC gene has been cloned, and over 140 disease-causing mutations have been identified. GLD has also been identified in a number of animal species, which can be used to examine pathogenic mechanisms and potential methods for treatment including gene therapy, stem cell therapy, and small molecule therapy.