Test Detail
Neuronal Ceroid Lipofuscinosis type 5 (NCL5) - Australian Cattle Dog and Border Collie
Neurological · Dog
Neuronal Ceroid Lipofuscinosis type 5 (NCL5) is a progressive lysosomal neurodegenerative disease affecting Australian Cattle Dogs and Border Collies. It is characterised by abnormal accumulation of lipofuscin (lipid waste pigment) in the neurons of the central and peripheral nervous system.\n\nThe disease produces progressive neurological deterioration with signs of cerebellar ataxia, cognitive dysfunction, behavioural abnormalities and vision loss. The course is inexorably progressive and leads to euthanasia or death generally between 2 and 5 years of age.
Incidence
- Australian Cattle Dog: the variant is uncommon; in the original study most genotyped dogs were reference homozygotes, with an occasional isolated carrier.\n- Border Collie: the mutation is present and screening is recommended in the breed.\n- Golden Retriever: different variant (2-bp deletion).\n- Exact carrier frequencies are not well established.
Breeder management
- Test the entire breeding line before the first mating.\n- Never mate two carriers with each other (25 % affected offspring).\n- An affected animal must not be bred.\n- A carrier can be mated to a clear animal; test the offspring intended for breeding.\n- Keep genetic records in the pedigree and consider testing in litters from carrier lines.
Specialist notes
The differential diagnosis includes: congenital cortical cerebellar dystrophy, hereditary cerebellar ataxia, viral encephalitis, toxoplasmosis, and other neurological diseases. The genetic test is the only definitive way to diagnose NCL5.\n\nThere is no treatment for NCL5. Management is supportive: antiepileptic medication for seizures, physiotherapy, nutritional management, and emotional support for the owner.\n\nThe progression is inexorable: the first signs appear at 1-2 years, the disease advances over 1-3 years, and euthanasia becomes the most humane option when quality of life deteriorates significantly.\n\nHealthy carrier dogs can have a completely normal life. The genetic test allows responsible breeding without the risk of producing affected animals.
References
1. Melville SA, Wilson CL, Chiang CS, Studdert VP, Lingaas F, Wilton AN. A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border collie dogs. Genomics 2005. PMID:16033706.
2. Kolicheski A, Johnson GS, O'Brien DP, et al. Australian Cattle Dogs with Neuronal Ceroid Lipofuscinosis are Homozygous for a CLN5 Nonsense Mutation Previously Identified in Border Collies. J Vet Intern Med 2016. PMID:27203721.
3. Villani NA, Bullock G, Michaels JR, et al. A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in Border Collies and Australian Cattle Dogs. Mol Genet Metab 2019. PMID:31101435.
4. Gilliam D, Kolicheski A, Johnson GS, et al. Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5. Mol Genet Metab 2015. PMID:25934231.
2. Kolicheski A, Johnson GS, O'Brien DP, et al. Australian Cattle Dogs with Neuronal Ceroid Lipofuscinosis are Homozygous for a CLN5 Nonsense Mutation Previously Identified in Border Collies. J Vet Intern Med 2016. PMID:27203721.
3. Villani NA, Bullock G, Michaels JR, et al. A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in Border Collies and Australian Cattle Dogs. Mol Genet Metab 2019. PMID:31101435.
4. Gilliam D, Kolicheski A, Johnson GS, et al. Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5. Mol Genet Metab 2015. PMID:25934231.