Neuronal ceroid lipofuscinosis, ARSG-related

Disease overview

The neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage diseases. Lysosomes digest and remove waste from the cells, so when they malfunction, large molecules build up in cells and cause neurological issues. NCL4A occurs from a deficiency in the activity of a lysosomal enzyme that is necessary for breaking down certain proteins in cells called Enzyme arylsulfatase G (ARSG). As a result, ARSG accumulates in the cells and affects the functionality of the brain and the nervous system. NCL4A is a progressive disease that affects American Staffordshire Terriers.

Gene name

ARSG

Inheritance

Autosomal recessive

Signs and symptoms

Affected dogs begin to display signs of neurological dysfunction between 3-5 years of age. These may include behavioral changes, lack of muscle coordination, difficulty jumping and balancing, abnormal gait (ataxia), seizures, and abnormal eye movement. This is a progressive disease, and symptoms of NCL4A often do not present until adulthood.

How is it diagnosed

A veterinarian will conduct a thorough exam, as well as review health history and any clinical signs. However, clinical signs are typically non-specific, requiring further testing, such as advanced imaging and/or spinal taps. Genetic testing can assist veterinarians with diagnosis and help breeders identify affected and carrier dogs. A definitive diagnosis of neuronal ceroid lipofuscinosis, however, is made post-mortem through necropsy of brain tissue.

Breeds at higher risk

Americal Staffordshire Terrier

Citations

Abitbol M, Thibaud JL, Olby NJ, Hitte C, Puech JP, Maurer M, Pilot-Storck F, Hédan B, Dréano S, Brahimi S, Delattre D, André C, Gray F, Delisle F, Caillaud C, Bernex F, Panthier JJ, Aubin-Houzelstein G, Blot S, Tiret L. A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14775-80. doi: 10.1073/pnas.0914206107. Epub 2010 Aug 2. PMID: 20679209; PMCID: PMC2930459.