Canine fucosidosis is an inherited lysosomal storage disorder caused by deficiency in alpha-L-fucosidase. Affected dogs develop clinical signs of ataxia, hypermetria and subtle alterations in behaviour by 12 months age and progress to severe motor and mental deterioration by 24-30 months of age. There is progressive cytoplasmic vacuolation in many viscera and peripheral and central nervous tissue. Early treatment with bone marrow transplantation halts progression of this disease providing encouragement that some aspects of the initial pathological changes may be reversible. This study aims to quantify the pattern of lysosomal storage and its impact on the brain and to correlate this with the neurological signs. We measured the degree of vacuolation using image analysis, quantified peri vascular storage and Purkinje cell loss in early affected (n=3), late affected (n=4) and control (n=9) tissues and examined glial fibrillary acid protein immunostaining for astrocytosis. Six different brain regions demonstrated widespread, severe vacuolation in advanced affected brain, with small changes in early disease which correlated well with the clinical signs of motor and mental dysfunction. There was a significant difference (F<0.001) between control and early affected and control and late affected. The storage in cortical perivascular regions increased with age (F<0.001). Purkinje cell numbers declined with advancing disease and astrocytosis was found in early affected brain. Further studies of the early lesions in fucosidosis to determine the impact of early immune and inflammatory responses to brain storage are needed to assist understanding of the disease process and the possibility of reversing these changes.
Gauthami Kondagari is a PhD student and veterinarian working on canine fucosidosis and its treatment. Her supervisor, Rosanne Taylor has demonstrated the effects of bone marrow transplantation, enzyme replacement and stem cell therapy of lysosomal storage disease.