| Description:
|
Ganglioside storage
diseases are defects of lysosomal hydrolase enzymes
that result in accumulation of gangliosides (glycosphingolipids
that are major constituents of plasma membranes in a
variety of cells, especially neurons) and glycolipid
substrates of these hydrolases within lysosomes of most
neurons throughout the nervous system, including brain,
spinal cord, and autonomic ganglia. The disease has
been described in a variety of species, including cats,
dogs, cattle, sheep, mice, and humans. In dogs, the
accumulation of ganglioside in the brain is due to deficiency
of acid beta-galactosidase. In most of the gangliosidoses,
total ganglioside content of the brain is high in clinically
affected animals. Asialo (sialic acid free) derivatives
of the gangliosides also accumulate in the brain and
liver. High levels of other neutral glycosphingolipids
may also be found. In some instances, different substrates
are stored in neural and visceral tissues, probably
reflecting the heterocatalytic activity of the deficient
enzyme. In affected Portuguese Water dogs, clinical
signs of GM1 are typically observed at around 4 to 5
months of age. In most cases, the disease is clinically
manifested as a neurodegenerative disorder. Common signs
of disease include vision problems, lethargy, difficulty
walking, and death in a period of approximately 8 months
to 1 year of age. |
| Inheritance: |
GM1 gangliosidosis
in Portuguese Water dogs shows an autosomal recessive
mode of inheritance; therefore two copies of the defective
gene, one inherited from each parent, have to be present
for a dog to be affected by the disease. Dogs with one
copy of the defective gene and one copy of the normal
gene - called carriers - show no symptoms but can pass
the defective gene onto their offspring. |
| DNA Test: |
A blood assay for
the diagnosis of GM1 gangliosidosis was developed in
the late 1980’s and has been the most accurate
method of detection of the disorder until recently.
This test allowed the detection of dogs affected by
GM1 gangliosidosis but failed to detect carriers of
this disease since they display no clinical symptoms.
Recently, a PCR–based assay for the detection
of GM1 gangliosidosis in Portuguese Water dogs became
available. This test implements the most recent advancements
in molecular diagnostics by selectively targeting the
gene associated with GM1 gangliosidosis. Using the PCR,
this gene can be detected, amplified, and analyzed to
determine whether a dog is affected (homozygous recessive)
or a carrier of the disease. Since the gene for GM1
gangliosidosis is directly targeted by this method,
results are 100% accurate. Breeders and veterinarians
can use this test to diagnose GM1 gangliosidosis, as
well as screen for carriers of the disease to help ensure
a healthy breeding line.
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