Globoid cell leukodystrophy
Globoid cell leucodystrophy (Galactocerebrosidase deficiency, Galactosylceramide lipidosis, Krabbe disease) is an autosomal-recessive genetic lysosomal storage disease that results in neurological disease of dogs characterized by peripheral nerve, spinal cord and cerebellar dysfunction.
This condition is caused by defective mutation in the gene encoding galactocerebrosidase which is responsible for lysosomal hydrolysis of specific galactolipids found primarily in myelin. Mutations in this gene (GALC gene (14q31)) are the result of numerous nonsense, missense, small insertion and small deletion mutations spanning the entire length of the gene.
A breed predisposition for this lysosomal storage disease has been reported in the Cairn Terrier, West Highland White Terrier, Miniature Poodle, Irish Setter, Bluetick Coonhound and Australian Kelpie.
Clinically affected dogs are often young (3 - 18 months of age) and present with poor weight gain, progressive peripheral neuropathy including ataxia, leg crossing, tremors and paresis which worsens with exercise.
Behavioral changes, blindness, dementia, anorexia, cachexia, urinary incontinence and quadriparesis are usually present in terminal stages of the disease with death occurring 2 - 6 months after onset of clinical signs, necessitating euthanasia.
A diagnosis is usually based on the clinical evaluation, neurological testing, histochemical and ultrastructural features. Additional testing includes brainstem auditory evoked response, peripheral nerve conduction velocity, repetitive stimulation, F wave analysis, electromyography and MRI imaging.
Histological examination of the central nervous system usually reveals diffuse, bilateral and symmetrical white matter lesion consisting of varying degrees of demyelination and axonal degeneration. extensive chromatolytic degeneration of neurons and moderate secondary Wallerian-type degeneration in the spinal cord and brain stem.
There is no known treatment for this condition, and use of corticosteroids and other drugs appears ineffective at halting disease progression.
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