Juvenile Addison´s disease (JADD)

Addison’s disease (hypoadrenocorticism) is caused by insufficient production of vital hormones by the adrenal cortex. These include glucocorticoids, which influence metabolism and immune function, among other processes, as well as mineralocorticoids, which are important for regulating sodium and potassium balance. Typical clinical signs include fatigue and weakness, loss of appetite, vomiting and diarrhoea, as well as a generally poor state of health.

In the Nova Scotia Duck Tolling Retriever, a particular form of the disease has been described that can occur at a young age. Affected dogs usually develop the disease within the first year of life. The average age at onset is approximately 5 months, although symptoms have also been observed in very young puppies and in dogs up to 12 months of age.

As many affected dogs showed additional health problems, the condition does not appear to be limited solely to the adrenal glands. In particular, immune-mediated concurrent diseases have been described, including blood disorders such as haemolytic anaemia and thrombocytopenia, inflammatory diseases of the intestine or joints (polyarthritis), thyroid disease (hypothyroidism), and inflammation of the oral cavity (stomatitis). Eye conditions such as conjunctivitis and uveitis have also been observed. JADD is therefore thought to be part of a multiple autoimmune syndrome (MAS) with variable clinical severity.

The clinical diagnosis of Addison’s disease is usually made using an ACTH stimulation test. This test assesses whether the adrenal glands produce sufficient cortisol following hormonal stimulation. In affected dogs, this response is reduced or absent. They generally require lifelong hormone replacement therapy. Any concurrent diseases may also require specific treatment.

A genetic variant in the RESF1 gene has been identified that is associated with JADD in the Nova Scotia Duck Tolling Retriever. The variant is inherited in an autosomal recessive manner with incomplete penetrance. Dogs carrying two copies of the variant have a significantly increased risk of developing the disease, although not every homozygous dog will develop clinical signs. In a UC Davis study, penetrance was estimated at approximately 76%.

In addition, individual dogs with early-onset Addison’s disease have been described in which the RESF1 variant was not present in the homozygous state. This suggests that other, as yet unidentified genetic causes of Addison’s disease may also play a role in the Nova Scotia Duck Tolling Retriever.

The genetic test can determine whether a dog is clear (N/N), carries the variant as a carrier (N/JADD) and can pass it on to its offspring, or is homozygous (JADD/JADD) for the variant tested and therefore has an increased risk of developing the disease.

Genetic testing enables targeted breeding decisions and can help reduce the risk of affected offspring without the need to exclude carriers from breeding altogether.