What is ... ?:

This is a storage disease, one of a relatively rare, but devastating, 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.

This is a similar condition to Krabbe's disease in people.

How is ... inherited?:

This is a rare disorder that is seen most often in the Cairn and West Highland white terriers, in which it is inherited as an autosomal recessive trait. It is also autosomal recessive in the miniature poodle, Irish setter and Australian kelpie. The mode of inheritance is unknown in other breeds.

What breeds are affected by ... ?:

What does ... 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. 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 and is invariably fatal. Affected dogs generally die or are euthanized by about 12 months.

How is ... 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 DNA test available through HealthGene that will identiify normal, carrier (heterozygous) and affected Cairn terriers and Westies. A DNA test is also available in some other breeds. See the Orthopedic Foundation of America's currently available tests for more information.

How is ... 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.

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.

An enzyme assay is available for galactocerebrosidase activity, which will show significantly decreased enzyme activity in affected animals (homozygous) and about 50% of normal activity in carriers (heterozygous), compared with homozygous normal dogs. A biopsy of affected peripheral nerves will show segmental demyelination and perivascular "globoid cells" (large foamy macrophages containing myelin debris).

Breeding advice:

Affected animals and their parents (who are carriers of the defective gene) should not be bred. There is a DNA test available through HealthGene that will identiify normal, carrier (heterozygous) and affected Cairn terriers and Westies. A DNA test is also available in some other breeds. See the Orthopedic Foundation of America's currently available tests for more information.
FOR MORE INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.

Resources:

Coates JR, O'Brien DP. Inherited peripheral neuropathies in dogs and cats. Vet Clin North Am Small Anim Pract 2004; 34:1361-1401.
Packer RA. Storage diseases. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:1041-1043.

galactocerebrosidosis

Globoid cell leukodystrophy (galactocerebrosidosis)