Canine fucosidosis: clinical findings

Abstract

The clinical course of canine fucosidosis, a neurovisceral lysosomal storage disease, is described from observations of 31 affected English Springer Spaniels. The diagnosis of fucosidosis was suggested by the development of multifocal neurological signs in the second year of life and confirmed by a deficiency of alpha‐L‐fucosidase activity in plasma and leucocytes. The progressive motor and mental deterioration was similar in all dogs and no affected animal survived to four years of age. Alpha‐L‐fucosidase activity in plasma was <0·05 μ/1 in all cases. The activity in leucocytes and other tissues was < 5 per cent of that of normal dogs. Vacuolated leucocytes occurred in cerebrospinal fluid, blood and bone marrow. The enlargement of peripheral nerves which is observed at autopsy could be detected by palpation of the ulnar nerve in advanced disease, however the results of electrodiagnostic studies were within normal limits. The clinical signs and pathological changes were found to be remarkably consistent from case to case making it an excellent model for investigating therapeutic strategies in human lysosomal storage disorders.

Associations between neurologic dysfunction and lesions in canine fucosidosis

“…This suggests that brain stem, spinal cord, peripheral and cranial nerve pathways, while exhibiting similar pathology, are less susceptible to the neurodegenerative effects of lysosomal expansion and inflammation. Similarly, while storage is extensive in autonomic nerves, particularly the vagus, signs of autonomic dysfunction such as dysphagia and regurgitation have not been consistently observed, even in severe fucosidosis (Taylor et al ).…”

“…A canine fucosidosis neurologic dysfunction score (NDS) incorporating signs of motor, behavioral and sensory dysfunction was developed by performing and documenting neurologic exams repeated at regular intervals on the earliest cases of fucosidosis in English Springer spaniels (Hartley et al ; Taylor et al ). To identify a threshold for the appearance of initial signs, and later emergence of distinctive signs indicating disease progression, NDSs collected on 53 canine fucosidosis cases from 1979 to 2009 were interrogated with statistics.…”

Oligodendrocyte Loss During the Disease Course in a Canine Model of the Lysosomal Storage Disease Fucosidosis

“…Central nervous system (CNS) myelin loss is an early pathological feature of infantile onset cases (1-4) and myelin abnormalities were identified by magnetic resonance imaging in the cerebellum and cerebrum of an 8-month-old child with fucosidosis (4). In canine fucosidosis, CNS myelin loss in the cerebellum and cerebrum is detectable from 8 weeks of age, many months prior to the first neurologic signs (5, 6). By 16 weeks, myelin deficits are more severe in the earlier myelinating tracts of the cerebellum compared to the later maturing corpus callosum of the cerebrum (5); however, clinical signs of anxiety and learning delay are inconsistent.…”

“…By 16 weeks, myelin deficits are more severe in the earlier myelinating tracts of the cerebellum compared to the later maturing corpus callosum of the cerebrum (5); however, clinical signs of anxiety and learning delay are inconsistent. Fine proprioceptive deficits and poorly modulated postural adjustments possibly caused by neuron loss and conduction deficits from hypomyelination in large, fast conducting sensory and motor tracts do not manifest in fucosidosis-affected dogs until considerably later, at 8 to 12 months of age (5, 6). At this time, white matter tracts show dispersion of myelinated axons and infiltration of vacuolated macrophages in addition to 21% loss of myelin relative to age-matched controls (5).…”

Canine α-l-fucosidase in relation to the enzymic defect and storage products in canine fucosidosis

“…The consistent clinical and pathological features in affected animals make it an excellent model for human fucosidosis and for evaluating experimental forms of enzyme replacement therapy, such as bone-marrow transplantation (Taylor et al, 1986a,b). Although both human and canine fucosidosis result from a similar deficiency ofa-L-fucosidase, there are differences in the clinical signs and cellular involvement in the two forms of the disease (Durand et al, 1982;Alroy et al, 1985;Taylor et al, 1987). In particular, the structures and tissue distribution of the storage products are different (Abraham et al, 1984;Alroy et al, 1985).…”