What is Globoid Cell Leukodystrophy / Krabbe’s Disease in dogs?

Globoid Cell Leukodystrophy(GCL) is known by a number of different names including Krabbe’s Disease and Galactocerebrosidosis. It is a very severe disease that affects the nervous system. Essentially, the condition arrises from the deficiency of a nervous system enzyme called galactocerebrosidase (GALC) that leads to the white matter of the nervous system degenerating. This white matter is the insulating matter or myelin that surrounds the nerve fibres and brain cells. When this insulating matter is broken down the nerve impulses can go in different directions than they normally would causing the message to get lost. This leads to a breakdown in the neurological function of the dog. An analogy would be to remove the insulation around wires in a fuse box and allow the electrical current to flow to where it wanted. The system would short circuit and breakdown very quickly.

Genetics of Globoid Cell Leukodystrophy

Globoid Cell Leukodystrophy is an autosomal recessive inherited disease meaning that an affected dog must have 2 defective copies of the gene responsible. In this case the gene that is responsible is the GALC gene (14q31) responsible for the manufacture of the enzyme galactocerebrosidase.

What is the severity of Globoid Cell Leukodystrophy?

Unfortunately, Globoid Cell Leukodystrophy is a very severe disease as it quickly reduces the quality of life for affected dogs as well as condemning the dog to a very short life. This disease has no cure.

What are the symptoms of Globoid Cell Leukodystrophy in dogs?

The symptoms of this devastating disease begin to show themselves early in the affected dog’s life from about 3 – 12 months of age. While there is some variation in the number and type of symptoms seen between individual dogs, there is the same pattern of worsening symptoms as the disease progresses. This is believed to be directly linked to the degeneration of the myelin surrounding the nerve fibres (dendritic cells). Symptoms of Globoid Cell Leukodystrophy include tail tremors, loss of control of the hindquarters, stumbling, weakness, lack of coordination, poor weight gain or even weight loss, reduced muscle tone and muscle degeneration and behavioural changes. These symptoms will increasingly worsen within a short time of about 2 – 6 months with most owners of affected dog electing to euthanize their affected dog before life becomes too difficult for their dog.

Diagnosis of Globoid Cell Leukodystrophy

An almost definitive diagnosis of Globoid Cell Leukodystrophy was limited to an assay test to assess the level of galactocerebrosidase (GALC) enzyme in white blood cells. Other methods of diagnosis have been used in the past including histochemical testing, clinical evaluation, MRI imaging and neurological testing, but the development of a DNA test for this disease will give a very definitive answer as to whether the dog is indeed affected by Globoid Cell Leukodystrophy. This DNA diagnostic tool will also confirm if a dog is a carrier or clear of this disease.

Treatment of dogs with Globoid Cell Leukodystrophy

Unfortunately, there are no real treatments that are effective in even slowing down the progression of this lethal inherited disease and no cure is available. Corticosteroids and some other drugs have been tried to slow the progression of Globoid Cell Leukodystrophy but without success. Prevention is by far the best option for reducing the number of dogs affected by Globoid Cell Leukodystrophy and modern DNA Disease Screening is available to help breeders make choices to prevent this disease in their puppies.

References

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Chen YQ et al (1993) Cloning and expression of cDNA encoding human galactocerebrosidase, the enzyme deficient in globoid cell leukodystrophy. Hum Mol Genet 2:1841–1845
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