related terms: Krabbe's disease, galactocerebrosidosis
What is globoid cell leukodystrophy?
This is a storage disease, one of a relatively rare group of disorders in which there is a deficiency of a particular enzyme necessary for normal metabolic processes within the body. The result is an accumulation in cells ("storage") of whatever product the enzyme normally acts upon. Typically, animals with a storage disease are normal at birth, fail to grow as rapidly as littermates, and at a consistent age, develop progressive signs of a disorder of the nervous system which will ultimately be fatal.
In globoid cell leukodystrophy (GCL), the lack of the enzyme ß-galactocerebrosidase results in an accumulation of galactocerebroside, a component of myelin. This disrupts the cells that normally produce myelin, a fatty substance that coats nerve cells, serves as an electrical insulator and is crucial to the normal conduction of nerve impulses. The progressive loss of myelin in the white matter tracts of the nervous system (brain, spinal cord and/or peripheral nerves) causes a variety of clinical signs such as lack of coordination, tremors, and weakness.
Krabbe's disease is a similar condition in people.
How is globoid cell leukodystrophy inherited?
This is an autosomal recessive disorder in the Cairn and West Highland white terrier.
What breeds are affected by globoid cell leukodystrophy?
This is a rare condition that is seen most often in the Cairn and West Highland white terrier.
It has also been reported (on a sporadic basis) in the beagle, miniature poodle, basset hound, pomeranian, and blue tick hound.
For many breeds and many disorders, the studies to determine the mode of inheritance or the frequency in the breed have not been carried out, or are inconclusive. We have listed breeds for which there is a consensus among those investigating in this field and among veterinary practitioners, that the condition is significant in this breed.
What does globoid cell leukodystrophy mean to your dog & you?
Puppies affected with GCL are normal at birth but grow more slowly than their littermates, and begin to to show signs of incoordination by 3 to 6 months. (In basset hounds the signs are seen later, between 1.5 and 4 years of age.) You may see tremors, a stiff gait, weakness, poor balance (falling to one side, stumbling), changes in behaviour or attitude, and vision changes.
The disease is rapidly progressive over a few months in Cairn and West Highland white terriers. GCL is invariably fatal, and affected dogs generally die or are euthanized before adulthood. The progression is slower in miniature poodles, over 2 to 4 years.
How is globoid cell leukodystrophy diagnosed?
Your veterinarian will do a thorough neurologic exam on your dog. Diagnostic tests for other conditions that might cause your dog's signs will show no abnormalities. As the disease progresses, magnetic resonance imaging (if available) will show diffuse disease in the white matter. There is a also a specific blood test available for GCL, from 1 American laboratory.
For the veterinarian: Initially there is an ascending ataxia and paraparesis, starting in the hind end, with or without cerebellar signs. There is a steady progression to paralysis +/- convulsions.
A heparinized blood sample may be sent to Jefferson Medical College, Division of Medical Genetics, in Philadelphia to test for GCL. Mean enzyme activity in affected dogs is 15-18% of normal, while heterozygous carriers have about 50% normal enzyme activity.
Biopsy of affected peripheral nerves will show segmental demyelination and perivascular "globoid cells" (large foamy macrophages containing myelin debris).
How is globoid cell leukodystrophy treated?
Unfortunately there is no treatment for this condition. Your veterinarian will help you decide when your dog's condition has deteriorated to the point where euthanasia is the best option.
Affected animals and their parents (who are carriers of the defective gene) should not be bred. It is possible to test apparently unaffected siblings to see if they are carriers (via DNA genetic marker or enzyme assay). The Institute for Genetic Disease Control in Animals http://www.vetmed.ucdavis.edu/gdc/gdc.html maintains an open research database for GCL in the Cairn and West Highland white terrier.
FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.
Ackerman, L. 1999. The Genetic Condition: A Guide to Health Problems in Purebred Dogs. pp 103-104. AAHA Press. Lakewood, Colorado.
March, P.A. 1996. Degenerative brain disease. Vet. Clin. of N.A. Small Animal Practice. 26(4): 945-971.
Copyright © 1998 Canine Inherited Disorders Database. All rights reserved.
Revised: October 30, 2001.This database is a joint initiative of the Sir James Dunn Animal Welfare Centre at the Atlantic Veterinary College, University of Prince Edward Island, and the Canadian Veterinary Medical Association.