Lysosomal storage disease (LSD)

General description

Lysosomal storage diseases (LSDs) are a diverse group of inherited disorders characterised by progressive neurological symptoms. A genetic variant in the gene CNP is causing lysosomal storage disease in Dalmatian dogs. Dogs which are homozygous for the genetic variant show first symptoms like slowly progressing abnormal behaviour, cognitive decline, loss of coordination and apparent visual impairment at the age of 18 months. At the age of 7 years difficulties with balance can be seen as well as signs of disorientation. Some heterozygous affected dogs exhibit a later-onset neurological disorder. In the breed Doberman, a genetic variant in the MAN2B1 gene was found to be responsible for the lysosomal storage disease. First symptoms could be noticed in an affected dog very early at around 2 months including clumsiness and difficulties in standing with frequent falls. Over the course of the disease progression, behavioural abnormality and difficulties with coordination and neurological symptoms occurred. In Weimaraner dogs, a different genetic variant in the CNP gene causes lysosomal storage disease. Clinical signs were first observed at about 4 years of age, are slowly progressive and include drowsiness, signs of paralysis, ataxia of the hind legs, increased tendency to fall, worsening faecal incontinence, cognitive decline, lack of coordination, loss of interest in food, changes in posture and episodes of trance-like behaviour become apparent. Due to the worsening of the neurological signs, euthanasia has to be considered.

Breeds

Dalmatian, Dobermann, Weimaraner

Lysosomal storage disease (LSD) – Doberman

In the breed Doberman, a genetic variant in the MAN2B1 gene was found to be responsible for the lysosomal storage disease. First symptoms could be noticed in an affected dog very early at around 2 months including clumsiness and difficulties in standing with frequent falls. A neurological examination revealed slightly obtunded mentation, proprioceptive ataxia, asymmetric reduced menace response and moderate divergent strabismus.

Over the course of the disease progression, aggressiveness towards other dogs, intolerance of grooming and bathing, compulsive behaviour like circling and inappropriate vocalization as well as uncoordinated movements and difficulties in navigating stairs developed.

Due to the progression of neurological signs, including dementia and apparent hallucinatory behaviour characterized by reactions to non-apparent stimuli or open areas/empty spaces, the affected dog was euthanized at the age of 14 months.

Lysosomal storage disease (LSD) – Weimaraner

In Weimaraner dogs, a different genetic variant in the CNP gene causes lysosomal storage disease.

Clinical signs were first observed at an age of about 4 years, are slowly progressive and include drowsiness, signs of paralysis, ataxia of the hind legs, increased tendency to fall, worsening faecal incontinence, cognitive decline, lack of coordination, loss of interest in food, changes in posture and episodes of trance-like behaviour.

Due to the worsening of the neurological condition, euthanasia has to be considered.

Lysosomal storage disease (LSD) – Dalmatian

In Dalmatian dogs, a lysosomal storage disease is caused by a genetic variant in the gene CNP.

Homozygous affected dogs show slowly progressing symptoms like abnormal behaviour, cognitive decline, loss of coordination, apparent visual impairment, anxiety, pacing and circling, hypersensitivity, sleep disturbance and loss of control over urination and defecation. First symptoms become apparent at the age of 18 months. At the age of about 7 years, difficulties with balance can be seen as well as signs of disorientation. The dogs tip over while walking, walk into obstacles and often lean against objects for support. Magnetic resonance imaging of these dogs showed marked generalized brain atrophy with pronounced white matter degeneration.

Dogs that are heterozygous for the variant can show later-onset neurological disorders. The symptoms are also progressive but less severe and develop at the age between 9 and 11 years. Clinical signs include loss of appetite, ataxia, restlessness or sleep disturbance. At the age of about 12 years, some dogs exhibit significant loss of coordination; they fall over and have difficulties standing up again. Some dogs also show signs of visual and hearing impairment.