Clinical Information

Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive disorder caused by a deficiency of galactocerebrosidase. A deficiency of this enzyme leads to an accumulation of galactocylceramide causing severe demyelination throughout the brain. Krabbe disease is primarily caused by mutations in the GALC gene, and it has an estimated frequency of 1 in 100,000 births. Although rare, a few infants with an early onset Krabbe disease phenotype due to deficiency of saposin A (SAP-A) have been found. Saposin-A is a sphingolipid activator protein that assists galactocerebrosidase in its action on galactosylceramide.

Severely affected individuals typically present between 3 to 6 months of age with increasing irritability and sensitivity to stimuli. Rapid neurodegeneration including white matter disease follows with death usually occurring by age 2. A small subset of individuals have later onset forms of the disease that are characterized by ataxia, vision loss, weakness, and psychomotor regression presenting anywhere from age 6 months to the seventh decade of life. The clinical course of Krabbe disease can be variable, even within the same family.

Newborn screening for Krabbe disease has recently been implemented in some states. The early (presymptomatic) identification and subsequent testing of infants at risk for Krabbe disease may be helpful in reducing the morbidity and mortality associated with this disease. While treatment is mostly supportive, hematopoietic stem cell transplantation has shown some success if performed prior to onset of neurologic damage.

Reduced or absent galactocerebrosidase in fibroblasts or leukocytes (CBGC / Galactocerebrosidase, Leukocytes) can indicate a diagnosis of Krabbe disease, however a number of polymorphisms in the GALC gene have been identified that result in reduced galactocerebrosidase activity in vitro, but by themselves do not cause disease. Molecular sequencing of the GALC gene (KRABZ / Krabbe Disease, Full Gene Analysis and Large [30 kb] Deletion, PCR) allows for detection of the disease-causing mutations in affected patients and carrier detection in family members.