GM1 Gangliosidosis Portuguese Water Dog Type
GM1 Gangliosidosis Portuguese Water Dog Type is a congenital lysosomal disorder affecting the Portuguese Water Dog breed. It is a progressive neurodegenerative disorder with a fatal outcome. GM1 belongs in a group of lysosomal disorders known as gangliosidosis, caused by the accumulation of lipids gangliosides. In the gangliosidoses group of disorders, other than GM1, belongs another disorder type, known as GM2. There are three forms of GM1: early infantile, late infantile, and adult. Except in Portuguese Water Dogs, GM1 has been reported in Friesian cattle, Siamese and Korat cats, English springer spaniels, and mixed breed beagle dogs.
Beta-galactosidase is a hydrolase enzyme located in the lysosomes. It catalyzes breakage of a glycosidic bond, resulting in the hydrolysis of beta-galactosides into monosaccharides. When the gene encoding for beta-galactosidase enzyme is deficient, abnormal storage of acidic lipid materials in cells of the central and peripheral nervous system occurs. GM1 is characterized by low or absent activity of this enzyme in brain and liver.
Characteristics and Symptoms
The first symptoms occur between 5 to 6 months of age. Incorrect function of cerebellum in affected dogs results in progressive neurological degradation and asymmetric growth. Dogs shows loss of coordination, muscle tremors, muscle ataxia, loss of weight and wide-based gait. The disorder may have an impact of the dog’s eyes as well, due to lesions of the retina and clouding of the cornea. Degenerative eye changes will be first seen as squinting and in end will progress to complete blindness. Behavioral changes will be present as well. Microscopic examination reveals occasional swollen axons and demyelinated fibers in white matter. These findings were most numerous in the cerebellum, corpus callosum and internal capsule in the brain, and all white matter tracts of the spinal cord. Examination of ultrastructure of swollen axons shows increased numbers of intact and degenerating mitochondria, membrane-bound dense or vacuolated bodies, and occasional inclusions.
Due to severity and progressive nature of the disorder, dogs are usually euthanized due to humane reasons or die by the age of 1 year.
GM1 Gangliosidosis Portuguese Water Dog Type is caused by deleterious mutations in the GLB1 gene encoding for lysosomal enzyme β -galactosidase. GM1 is inherited as an autosomal recessive disorder. The dog can be clear, carrier or affected. Healthy parents of an affected puppy are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the GM1. At conception, when mating two carrier dogs, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Wang ZH, Zeng B, Shibuya H, Johnson GS, Alroy J, Pastores GM, Raghavan S, Kolodny EH. Isolation and characterization of the normal canine beta-galactosidase gene and its mutation in a dog model of GM1-gangliosidosis. J Inherit Metab Dis. 23 (2000) 593-606.