Lysosomal storage disease in Dalmatians

Lysosomal storage disease is a neurodegenerative disorder. It shares similarities with neural ceroid lipofuscinosis but is a distinct entity with distinct pathological features. The disease is characterized by the accumulation of autofluorescent inclusions in lysosomes in the cerebral cortex, cerebellum, optic nerve, and cardiac muscle.

Clinical manifestations are progressive and primarily involve the central nervous system. In Dalmatians, the first neurological signs appear around 18 months of age and gradually worsen. These include anxiety, restlessness, circling, hypersensitivity, cognitive decline, sleep disorders, loss of coordination, urinary and fecal incontinence, and visual disturbances.

The cause of the disease in Dalmatians is the c.1107del mutation in the CNP gene. The mutation leads to disruption of myelin integrity and accumulation of autofluorescent material in lysosomes.

Inheritance is described as autosomal, incompletely dominant with variable expressivity. Heterozygous individuals who inherit mutation from only one parent may have milder, later-onset, or variable clinical signs. In contrast, homozygotes who inherit mutation from both parents usually show a more severe or earlier-onset form of the disease. The manifestations of the disease therefore depend on the genotype as well as the individual expressivity and penetrance of the mutation.

A genetic test can clearly reveal the genotype of the animal and is a suitable tool for breeders to avoid unintentional breeding of affected puppies.

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References:

Bullock, G., Johnson, G.S., Mhlanga-Mutangadura, T., Petesch, S.C., Thompson, S., Goebbels, S., Katz, M.L. : Lysosomal storage disease associated with a CNP sequence variant in Dalmatian dogs. Gene 830:146513, 2022. Pubmed reference: 35447247