Globoid cell leukodystrophy in West Highland White Terriers and Cairn Terriers

Globoid cell leukodystrophy (GLD, Krabbe disease) is a severe lysosomal inherited storage disease caused by insufficient function of galactocerebrosidase (GALC). GALC is responsible for lysosomal catabolism of some galactolipides, incl. galactocerebroside (= galactosylceramide) and psychosine. Due to insufficient function of GALC the galactosylceramide is not correctly metabolized and is accumulated in cells producing myelin. Myelin creates protective sheath around the nerve cells and ensures fast transmission of nerve impulses. The myelin deficiency caused by accumulation of galactosylceramide results in degeneration of the nervous system.
Globoid cellular leukodystrophy (Krabbe disease) is a severe disease occurring in humans. GLD was also found in West Highland White Terriers (WHWT) and Cairn Terriers. GLD occurs less often in Beagles, Miniature Puddles, Blue Tick Hound, Pomeranian, Basset, Kelpie and Irish Setter.
Humans and dogs affected with insufficient function of GALC have characteristic pathological findings in nervous system - abnormal presence of globoid cells, having usually more than one cell nucleus.
In WHWT and Cairn Terriers, a point substitution c.473A>C was found during testing, which is responsible for insufficient function of GALC.
GLD occurs in puppies as early as 1 to 3 months after birth. The first symptoms include tremor of limbs, subsequent muscle atrophy and neurological degeneration of brain white matter and spinal cord. Dogs can survive 8 to 9 months when the signs become unbearable and the dogs are euthanized.

GLD is inherited recessively. Dogs carrying two copies of the mutated gene (P/P) are affected with the disease, but do not show any external signs affecting their health. If two heterozygous (N/P) individuals are mated, theoretically there will be 25% healthy offsprings (N/N), 50 % offsprings will be carriers of the disease (N/P) and 25 % inherit the mutated allele from both parents and will be affected with GLD (P/P).

Reference:

Wenger, D.A. et al.: Globoid cell leukodystrophy in cairn and West Highland white terriers Journal of Heredity 90:138-142, 1999

Fletcher, JL. Et al.: Clinical signs and neuropathologic abnormalities in working Australian Kelpies with globoid cell leukodystrophy (Krabbe disease). J Am Vet Med Assoc 237:682-8, 2010
McGraw, RA et al. : Molecular basis of globoid cell leukodystrophy in Irish setters. Vet J 171:370-2, 2006