Fucosidosis

From Dog

Fucosidosis is an autosomal-recessive genetic lysosomal storage disease of the English Springer Spaniel dog that is progressive and invariably fatal[1].

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[2] which leads to a complex neurodegenerative cascade of vacuolation, neuroinflammation, neuronal loss and myelin deficits in the cerebral cortex[3][4]. 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[5].

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[6]. Acrosomal dysgenesis and impaired sperm maturation have been reported in affected male dogs while female dogs appear fertile[7].

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[8].

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[9].

Diagnosis is based on presenting clinical signs, histological examination of lymphoid tissue and PCR testing[10].

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[11][12].

References

  1. Skelly BJ et al (1996) The molecular defect underlying canine fucosidosis. J Med Genet 33(4):284-288
  2. Abraham D et al (1984) The enzymic defect and storage products in canine fucosidosis. Biochem J 221:25-33
  3. Fletcher JL et al (2011) Myelin genes are downregulated in canine fucosidosis. Biochim Biophys Acta 1812(11):1418-1426
  4. Kondagari GS et al (2011) Investigation of cerebrocortical and cerebellar pathology in canine fucosidosis and comparison to aged brain. Neurobiol Dis 41(3):605-613
  5. Kondagari GS et al (2011) Canine fucosidosis: a neuroprogressive disorder. Neurodegener Dis 8(4):240-251
  6. Herrtage ME (1988) Canine fucosidosis. Vet Annual 28:223-227
  7. Veeramachaneni DN et al (1998) Deficiency of fucosidase results in acrosomal dysgenesis and impaired sperm maturation. J Androl 19(4):444-449
  8. Smith MO et al (1996) Fucosidosis in a family of American-bred English Springer Spaniels. J Am Vet Med Assoc 209(12):2088-2090
  9. Ferrara ML et al (1997) Canine fucosidosis: a model for retroviral gene transfer into haematopoietic stem cells. Neuromuscul Disord 7(5):361-366
  10. Holmes NG et al (1998) A PCR-based diagnostic test for fucosidosis in English springer spaniels. Vet J 155(2):113-114
  11. Kondagari GS et al (2011) Treatment of canine fucosidosis by intracisternal enzyme infusion. Exp Neurol 230(2):218-226
  12. Bielicki J et al (2000) Recombinant canine alpha-l-fucosidase: expression, purification, and characterization. Mol Genet Metab 69(1):24-32