Galactosialidosis

Lysosomal storage disorders are a group of more than 40 heritable diseases that are caused by the marked deficiency of one or more lysosomal enzymes. This loss in enzymatic activity results in the progressive accumulation of waste products with the cell's lysosomes. This leads to cellular and tissue damage, subsequent organ dysfunction, and in some diseases to early mortality. Although the incidence of individual LSDs can be quite low, as a group they occur in approximately 1 in 7500 live births, and as such represent one of the more prevalent groups of genetic diseases in humans.

Galactosialidosis is a rare autosomal recessive disease with combined deficiency of two lysosomal enzymes (Beta-galactosidase and neuraminidasedue) to the lack of enzyme called Protective Protein/Cathepsin A (PPCA). These three enzymes work together to break down long sugar chains in the cell's lysosomes. Lack of cathepsin A protection results in breakdown and deficiency of these two enzymes, which, in turn, causes accumulation of lysosomal mucopolysaccharide. This deficiency leads to two neurodegenerative lysosomal storage disorders: sialidosis and galactosialidosis.

Signs

The principal clinical manifestations include abnormal bone formation, seizures, visual loss (with corneal clouding), heart valve diseases, progressive inability to coordinate voluntary muscular movements (ataxia), hearing loss and deteriorating mental ability. Bony changes are especially noticeable in the spine. Affected dogs may also have excessive fluid accumulation in the eyelids, and an increase in the size of the 'eyebrow' ridges above the eyes; discolored patches of skin; accumulation of watery fluid in the abdominal cavity and permanent bending of joints in the foot. There may be wart formation on the skin due to enlargement of surface blood vessels.

These clinical, biochemical and pathological findings in dogs are similar to those observed in human patients with adult-onset galactosialidosis. The disease is diagnosed using several kinds of laboratory tests.

Adult onset of the neurological signs of this disease has been described in Schipperke dogs.

Treatment of Galactosialidosis

Currently, treatments for these rare disorders are limited to bone marrow transplantation and enzyme replacement therapy (in humans). However, because enzyme therapy is only effective for those manifestations that do not involve the central nervous system (CNS). Therefore, other approaches, including the use of gene- and cell-based therapies that offer the opportunity for a more prolonged therapeutic effect than can be realized with enzyme replacement therapy, as well as the possibility of treating the CNS, are also being evaluated. Seizures can be especially difficult to control.