Neuronal Ceroid Lipofuscinosis 10, NCL 10

Common symptoms reflect central nervous system malfunction and include partial or total vision loss, behavior changes, abnormal gait, and seizures. Symptoms usually progress slowly over time.

Bulldogs homozygous for this mutation typically present between 1 and 3 years of age and the symptoms progress slowly over 2 to 4 years.

NCL is definitively diagnosed through genetic testing or examination of central nervous system (CNS) tissues after the affected dog is deceased. Clinical signs of this disease may mimic many other CNS diseases, so examination by a veterinarian or veterinary neurologist is required. Advanced imaging (CT or MRI scan) and/or spinal taps may be performed to rule out other diseases.

Currently, there is no treatment for NCL. While gene therapy trials in mouse models have proven promising, there is much more research required before it can be used in veterinary hospitals.

Talk to your vet about your dog’s NCL result so you can work together to plan ongoing care and monitoring. Note any changes in their coordination, mobility, or behavior.

Keep your dog’s environment calm and consistent. Use slings, harnesses, or supportive devices as needed to help with mobility, and place rugs or mats on slippery floors to prevent falls.

Encourage gentle, food-based activities such as treat searches or puzzle toys to help your dog stay mentally engaged without overexertion.

Help your dog feel secure by keeping furniture in familiar places, using non-slip mats, and maintaining predictable daily routines.

A mutation in the CTSD gene has been identified in American Bulldogs with NCL. CTSD encodes the protein Cathepsin D, a lysosomal enzyme that helps to break down proteins. Mutations in CTSD have been shown to cause NCL in a variety of species including humans, cows, and sheep. The mutation characterized in American Bulldogs leads to a significant but incomplete reduction in enzyme activity, which likely explains the slow progression of the disease compared to other forms of NCL.

Penetrance: This disease is inherited in an autosomal recessive manner, meaning that affected dogs must have two copies of the mutation to show clinical signs.

Gene

CTSD (Exon 5)

Inheritance type

recessive

Clinical category

Multisystem

Citations

1. Awano et al 2006

• American Bully
• Alapaha Blue Blood Bulldog
• American Bulldog
• Olde English Bulldogge