The disease results from a deficiency of the enzyme α-L-fucosidase and heterozygotes are without symptoms and possess fucosidase activities of approximately 50% of the control mean.
Pathology and clinical signs are the result of the lysosomal accumulation of fucose containing glycoconjugates which leads to a complex neurodegenerative cascade of vacuolation, neuroinflammation, neuronal loss and myelin deficits in the cerebral cortex. These changes, though absent at birth can be by 4 months of age, well before the clinical signs of motor dysfunction present at 10 - 12 months of age.
Clinical signs are mainly neurological symptoms in adolescent or adult dogs including progressive ataxia, proprioceptive difficulties, apparent blindness, change in temperament, dysphagia, dysphonia, and loss of learned behaviour. Acrosomal dysgenesis and impaired sperm maturation have been reported in affected male dogs while female dogs appear fertile.
As the disease progresses there is a rapid deterioration in body condition with muscle wasting. Affected dogs die or are euthanased by 3 to 4 years of age. Late onset of signs may result in misdiagnosis as a primary behavior problem or acquired neurologic disease.
Bone marrow transplantation and retroviral gene transfer has shown that haematopoietic stem cells can provide enzyme producing daughter cells to the central nervous system, altering disease course.
Diagnosis is based on presenting clinical signs, histological examination of lymphoid tissue and PCR testing.
Although there is no practical treatment for this condition, experimental use of monthly injections of recombinant canine α-l-fucosidase enzyme given intracisternally has shown promise in ameliorating clinical signs.
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