Neuronal Ceroid Lipofuscinosis 4a (NCL4a Dog)

Neuronal ceroid lipofuscinosis 4a (NCL4a) is a metabolic, neurodegenerative disease caused by a change of a single base pair in exon 2 of the ARSG gene. Ceroid lipofuscin, a waste product of the cell metabolism, is stored in the cells and not broken down further. It accumulates in the nerve cells of the retina and the brain. Affected animals therefore show symptoms such as visual disorders, balance disorders and later completely disorientated behaviour and physical degeneration.

The disease occurs in the American Staffordshire Terrier. The inheritance is autosomal recessive.

Synonym: lysosomal storage disease, cerebellar cortical abiotrophy

Symptoms

Visual disorders
Blindness
Balance disorders
Hunched posture
Behavioural changes
Disorientated behaviour
Physical degeneration

General Information

Neuronal ceroid lipofuscinosis 4a (NCL4a) is a metabolic, neurodegenerative disease.
Ceroid lipofuscin, a waste product of the cell metabolism, is stored in the cells and not broken down further.
This leads to deposits of ceroid lipofuscin in the brain and the retina.
The function of the nerve cells is thereby severely damaged.
The first disorders appear at the age of 3-5 years; the brain is affected increasingly a little later.
NCL4a cannot be treated; affected animals are euthanised 1-4 years after diagnosis.

Breeds affected

Staffordshire Terrier, a dog breed affected by neuronal ceroid lipofuscinosis type 4A (NCL4A)

American Staffordshire Terrier

Test Information

This mutation test detects a change of a single base pair (c.296G>A) in exon 2 of the ARSGgene.

Genotype and Lab Report

Inheritance: autosomal recessive

→ The disease only occurs if both alleles of the gene are affected by the mutation (ncl4/ncl4). Dogs that have only one allele with the causative mutation (N/ncl4) are clinically healthy carriers.

Genotypes:

N/N = genetically normal

The dog has no predisposition for NCL 4a and therefore cannot pass it on to its offspring.

N/ncl4 = a carrier

The dog is a clinically healthy carrier. The variation is passed on 50% to the offspring, which are also carriers.

ncl4/ncl4 = affected

The variation is passed on 100% to the offspring. The animals frequently do not reach breeding age.

Recommendations

Carrier animals can be bred to normal animals (N/ncl4 x N/N). Before using the offspring in breeding, it should be tested whether they are normal or carriers.
Mating two carrier animals (N/ncl4 x N/ncl4) should be avoided because there is a 25% chance that the offspring will be affected.
Affected animals (ncl4/ncl4) should be excluded from breeding if they reach breeding age.

Literature

Abitbol, M., Thibaud, J.L., Olby, N.J., Hitte, C., Puech, J.P., Maurer, M., Pilot-Storck, F., Hédan, B., Dréano, S., Brahimi, S., Delattre, D., André, C., Gray, F., Delisle, F., Caillaud, C., Bernex, F., Panthier, J.J., 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 107:14775-80, 2010. Pubmed reference: 20679209. Doi: 10.1073/pnas.0914206107.

Further information is available at Online Mendelian Inheritance in Animals.