Heterozygous carriers of galactocerebrosidase mutations that cause Krabbe disease have impaired microglial function and defective repair of myelin damage.

ABSTRACT: This review addresses two puzzling findings related to mutations in galactocerebrosidase (GALC) that cause Krabbe disease (KD), a severe lysosomal storage disorder characterized by extensive myelin damage in children with mutations in both GALC alleles. First, heterozygous carriers of KD-causing mutations, which include the biological parents of children with KD, exhibit increased risk for developing other diseases. Second, variants in the GALC locus increase the risk of developing multiple sclerosis (MS), another disease characterized by extensive myelin damage. What explains these correlations? In studies on cuprizone-induced myelin damage in heterozygous (GALC+/-) mice carrying one copy of a mutation that causes KD-like disease, the extent of damage was similar in GALC+/- and wild-type

SUBMITTER: Scott-Hewitt NJ 

PROVIDER: S-EPMC5900492 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature