Lysosomal storage disorder due to galactocerebrosidase (GALC) deficiency that accumulates psychosine and causes demyelination of the central and peripheral nervous system. In dogs, distinct GALC mutations are recognised in the Cairn Terrier and West Highland White Terrier (shared) and in the Irish Setter (independent). It is inherited in an autosomal recessive manner and is one of the natural models of human Krabbe disease.

The Cairn Terrier and West Highland White Terrier share the same mutation; the Irish Setter has an independent mutation. Population frequencies are not well published (limited data).

- Progressive ataxia with onset in the first months\n- Spasticity and tetraparesis\n- Proprioceptive deficits\n- Progression to a severe condition and euthanasia

Canine globoid cell leukodystrophy was one of the first natural models of human Krabbe disease, described in the Cairn Terrier and Irish Setter in the 1970s. The responsible GALC mutations in each breed were subsequently identified. The canine model has been fundamental in the development of gene therapy and enzyme replacement trials.

- Genotype breeding animals before mating\n- Do not cross two carriers: 25 % risk of affected homozygotes\n- Identify carriers so they are not mated with each other\n- Preserve genetic diversity when replacing carrier lines\n- Exclude affected animals from breeding

Differential diagnosis with other canine leukodystrophies (e.g. sphingomyelinase deficiency) and with degenerative ataxias of the young. The age of onset differs according to the mutation: earlier in terriers and somewhat later in the Irish Setter. Measurement of GALC activity in leukocytes confirms the deficiency.

1. Victoria T, Rafi MA, Wenger DA. 1996. Cloning of the canine GALC cDNA and identification of the mutation causing globoid cell leukodystrophy in West Highland white terriers (Genomics) (PMID 8661004).
2. Wenger DA, Victoria T, Rafi MA, Luzi P, Vanier MT, Valls JM, Patterson DF, Haskins ME. 1999. Globoid cell leukodystrophy in cairn and West Highland white terriers (J Hered) (PMID 9987921).
3. McGraw RA, Carmichael KP. 2006. Molecular basis of globoid cell leukodystrophy in Irish setters (Vet J) (PMID 16490723).
4. Wenger DA, Luzi P, Rafi MA. 2021. Advances in the diagnosis and treatment of Krabbe disease (Int J Neonatal Screen) (PMID 34449528).
5. OMIA:000578-9615 (Krabbe disease / globoid cell leukodystrophy, GALC, Canis lupus familiaris).