β-Mannosidosis in German Shepherd Dogs

Area of Science:

• Veterinary Neurology
• Canine Genetics
• Lysosomal Storage Diseases

Background:

• Neurological disorders in young animals can significantly impact welfare and breeding programs.
• Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders characterized by the accumulation of undigested material within lysosomes.

Observation:

• Three German Shepherd pups presented with failure to thrive, stiffness, reluctance to move, deafness, seizures, ataxia, and proprioceptive deficits.
• Histopathology revealed severe neuronal and glial vacuolation in the central nervous system, along with vacuolated macrophages in the spleen and liver.
• Vacuoles were devoid of storage material upon PAS and Sudan black staining, suggesting an oligosaccharidosis.

Findings:

• Biochemical and genomic analyses confirmed the condition as beta-mannosidosis (β-mannosidosis), a previously undiagnosed LSD in dogs.
• A specific mutation, c.560T>A in exon 4 of the MANBA gene, was identified as the cause of the disease.
• This autosomal recessive mutation results in an isoleucine to asparagine substitution in the beta-mannosidase enzyme, predicted to impair its function.

Implications:

• This study describes the first canine case of beta-mannosidosis, expanding the known spectrum of LSDs in domestic animals.
• Identification of the causative mutation provides a basis for genetic testing and potential carrier screening in affected German Shepherd lines.
• Understanding the canine model of beta-mannosidosis may offer insights into the human form of the disease and potential therapeutic strategies.