Juvenile neuronal ceroid lipofuscinosis of the Dachshund caused by a deficiency of the lysosomal protease TPP1 (CLN2). It accumulates curvilinear autofluorescent material in neurons and causes progressive neurodegeneration of juvenile onset. It is inherited in an autosomal recessive manner and is one of the natural models of human CLN2 disease.

Dachshund. The mutation is uncommon in the studied population (181 unrelated dogs, including 77 Dachshunds, all clear; Awano et al., 2006). No carrier frequency has been published.

- Onset around 9 months of age with vomiting, mental dullness and loss of learned behaviours\n- Disorientation and behavioural alterations\n- Ataxia and myoclonic seizures\n- Progressive visual impairment\n- Progressive course towards a severe condition and early death (around 12 months in the described cases)

The causal mutation was identified in a juvenile Dachshund: Awano and colleagues (2006) described a single-nucleotide deletion in exon 4 of TPP1 (c.325delC) that causes a frameshift and a premature stop codon. The Dachshund was thus established as a preclinical model for gene therapy and enzyme replacement of human CLN2. Late-onset NCL of the Tibetan Terrier is caused by ATP13A2 (CLN12), not by TPP1.

- Genotype breeding animals before mating\n- Do not cross two carriers: 25 % risk of affected homozygotes\n- Identify carriers so they are not mated with each other\n- Preserve genetic diversity when replacing carrier lines\n- Exclude affected animals from breeding

Differential diagnosis with other canine NCLs and with other juvenile encephalopathies; do not confuse with late-onset NCL of the Tibetan Terrier (ATP13A2/CLN12). Determination of TPP1 enzyme activity in blood or tissue confirms the deficiency.

1. Awano T, et al. A frame shift mutation in canine TPP1 (the ortholog of human CLN2) in a juvenile Dachshund with neuronal ceroid lipofuscinosis. Mol Genet Metab. 2006;89(3):254-260. PMID: 16621647
2. Katz ML, et al. Retinal pathology in a canine model of late infantile neuronal ceroid lipofuscinosis. Invest Ophthalmol Vis Sci. 2008;49(6):2686-2695. PMID: 18344450
3. Kohlschütter A, Schulz A. CLN2 disease (classic late infantile neuronal ceroid lipofuscinosis). Pediatr Endocrinol Rev. 2016;13(Suppl 1):682-688. PMID: 27491216