Lysosomal Storage Disease (LSD) (Lagotto Romagnolo)

 

Gene: ATG4D

Transmission: Autosomal recessive

For an autosomal recessive genetic disease, an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, ATG4D gene; c.1288 G>A, exon10

Breeds: Lagotto Romagnolo

Medical system: Neurological, lysosomal storage disease

Age of onset of symptoms: Variable, from several months to several years

Lysosomal Storage Disease (LSD), also called Lagotto Storage Disease, is a progressive neurodegenerative disease seen in the Lagotto Romagnola dog breed.  It is caused by an enzyme deficiency within lysosomes of the cell resulting in abnormal recycling and accumulation of cell products.  The nervous system is particularly susceptible, especially the cerebellum which coordinates muscle movements.  The first signs of the disease involve movement problems including clumsiness and abnormal eye movements (nystagmus), progressing to difficulty in walking (cerebellar ataxia).  Changes in behavior, including depression, restlessness and aggression are additional symptoms of the disease.  Age of onset of clinical signs is variable, from four months to four years, with an average of about two years.  Progression of the disease is also variable, from months to years.  Dogs with severe cases of the disease are often euthanized for humanitarian reasons.

 

References:
OMIA link: [1954-9615]

Stee K, Van Poucke M, Lowrie M, et al. (2023) Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med. [pubmed/37341581]

Syrjä P, Palviainen M, Jokinen T, et al. (2020) Altered basal autophagy affects extracellular vesicle release in cells of Lagotto Romagnolo dogs with a variant ATG4D. Vet Pathol 57:926-35. [pubmed/33016245]

Syrjä P, Anwar T, Jokinen T, Kyöstilä K, et al. (2017) Basal autophagy is altered in Lagotto Romagnolo dogs with an ATG4D mutation. Vet Pathol. 54(6):953-963.  [pubmed/28583040]
Kyostila K, Syrja P, Jagannathan V, et al. (2015) A missense change in the ATG4D gene links aberrant autophagy to a neurodegenerative vacuolar storage disease.  PLOS Genetics 11(4):e1005169. [pubmed/25875846]