Neuronal ceroid lipofuscinoses (NCL) are neurodegenerative lysosomal diseases characterized by the accumulation of ceroid lipofuscin (autofluorescent) in neurons and other tissues. The form described in the Golden Retriever is classified within type 5, related to the CLN5 gene. It produces progressive neurological deterioration with behavioral changes, ataxia, seizures and blindness, leading to death or euthanasia. There is no treatment and its control is based on avoiding crosses of carriers.

Rare disease, described mainly in Golden Retriever lines from North America and Europe. There are no reliable carrier frequency figures published in a consolidated manner (limited data). Its low current prevalence is explained in part by the use of the test in breeding animals of affected lines.

- Behavioral changes: aggression, anxiety, disorientation or excessive attachment
- Loss of learning and of response to known commands
- Progressive ataxia and incoordination of the four limbs
- Myoclonus, tremors and seizures
- Progressive visual deterioration up to blindness (retinal degeneration)
- Cachexia and general worsening in advanced stages
- Death or euthanasia usually before 4-6 years

NCL5 was first described in the Border Collie, where Melville et al. (2005) identified a nonsense mutation in CLN5 (c.619C>T; p.Gln206*). The same variant was later confirmed in the Australian Cattle Dog (Kolicheski et al. 2016). In the Golden Retriever, Gilliam et al. (2015) described a two-base-pair deletion in CLN5 (c.934_935delAG) that gives rise to an NCL5 phenotype specific to the breed. Therefore, the CLN5 test is not identical between the Golden and the Border Collie/Australian Cattle Dog breeds.

- Test breeding animals from lines with a history of early neurodegenerative disease
- Never cross carrier with carrier: 25% risk of affected puppies in each litter
- A carrier can be crossed with a clear individual, keeping only clear offspring for breeding if you seek to eliminate the allele
- In a young dog with behavioral changes and progressive ataxia, request neurological study and consider genetic testing
- Record the results alongside the pedigree and communicate them to the breed club

The differential diagnosis includes other canine NCLs, idiopathic epilepsy, non-ceroid storage diseases and inflammatory or degenerative encephalopathies. Classical confirmation relies on biopsy (PAS-positive and autofluorescent material in tissues) and today on the DNA test. There is no effective treatment; management is palliative (antiepileptics, environmental enrichment, control of household risks). Genetic counseling to the family of the index case is essential: both parents are carriers.

1. Gilliam D et al. 2015, deleción de dos pares de bases y cambio de marco en CLN5 en Golden retriever con NCL (PMID 25934231)
2. Kolicheski A et al. 2016, Australian Cattle Dogs con NCL son homocigotos para una mutación sin sentido de CLN5 previamente identificada en Border Collie (PMID 27203721)
3. Melville SA et al. 2005, una mutación en CLN5 canino causa lipofuscinosis neuronal ceroide en Border collie (PMID 16033706)
4. OMIA:001482 NCL5 (CLN5)