Lysosomal storage disorders (LSDs) are a group of more than 40 heritable diseases that are caused by the marked deficiency of one or more lysosomal enzymes. The loss in enzymatic activity results in the progressive accumulation of waste products within the cell's lysosomes. This leads to cellular and tissue damage, subsequent organ dysfunction, and, in some cases, to premature death. 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 common genetic diseases.
Galactosialidosis is a rare autosomal recessive disease with combined deficiency of three enzymes: beta-galactosidase, neuraminidase, and enzyme protective protein/cathepsin A (PPCA). The three enzymes work together to break down long sugar chains in the cell's lysosomes. This deficiency leads to two neurodegenerative lysosomal storage disorders, sialidosis and galactosialidosis. Adult onset of the neurological signs of this disease has been described in Schipperke dogs.
The principal clinical signs include abnormal bone formation, seizures, visual loss with corneal clouding, heart valve diseases, ataxia (progressive inability to coordinate voluntary muscular movements), 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 ridges above the eyes. Discolored patches of skin, accumulation of watery fluid in the abdominal cavity and permanent bending of joints in the foot are commonly seen. There may be wart formation on the skin due to enlargement of surface blood vessels. The 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. Treatments of human cases for these rare disorders are limited to bone marrow transplantation and enzyme replacement therapy, which is only effective for those manifestations that do not involve the central nervous system. Other approaches, including the use of gene- and cell-based therapies that offer the opportunity for a more prolonged therapeutic effect are also being evaluated. Seizures can be especially difficult to control.