Glycogenosis of the Curly-Coated Retriever due to deficiency of the glycogen debranching enzyme (AGL), which prevents complete degradation of glycogen and causes its abnormal accumulation in liver and muscle. It produces hepatomegaly, elevated liver and muscle enzymes, exercise intolerance and, over time, liver fibrosis and myopathy. It is inherited in an autosomal recessive manner. In this breed the course is relatively mild compared with other canine forms.

Affected breed: Curly-Coated Retriever. Carriers have been identified in the USA, New Zealand, Australia and Finland, but no reliable global population frequencies are published; the disease is rare and known within the breed.

- Early elevation of ALT, ALP and CK in the first year
- Hepatomegaly with increased hepatic glycogen
- Exercise intolerance, lethargy and collapse after exercise by around 14 months
- Increased glycogen in muscle with myofibril disruption/disorganisation
- Progressive liver fibrosis and myopathy with age
- Hypoglycaemia in stressful situations in some cases

GSD IIIa was identified in the Curly-Coated Retriever from dogs with hepatomegaly, biochemical alterations and exercise intolerance. Gregory and colleagues (2007) showed that debranching activity was undetectable in liver and muscle of affected dogs and, on sequencing the 33 exons of AGL, found a deletion of one adenine in exon 32 that causes a frameshift and a truncated protein. The mutation was homozygous in the affected dogs and heterozygous in the parents, and a carrier test was developed for the breed. Yi and colleagues (2012) subsequently characterised the canine model of the disease and confirmed the usefulness of the genetic test (PMID 17338148; PMID 22736456).

- Test Curly-Coated Retriever breeding animals with the AGL test (c.4223delA)
- Do not mate two carriers: 25 % risk of affected homozygotes
- A carrier can be mated to a clear animal; offspring intended for breeding must be tested
- Exclude affected animals from breeding and test parents and siblings of cases
- In carriers with good qualities, always mate to clear animals and test the offspring

Differential diagnosis with other glycogenoses (GSD Ia, GSD II/Pompe), hereditary myopathies and congenital liver diseases. Measurement of debranching activity in liver/muscle and the genetic test are confirmatory. Dietary management (high-protein diet, cornstarch) may improve exercise tolerance and liver function, without halting progression. Biochemical (ALT, AST, ALP, CK) and ultrasound follow-up recommended.

1. Gregory BL, Shelton GD, Bali DS, et al. Glycogen storage disease type IIIa in curly-coated retrievers. J Vet Intern Med 2007;21(1):40-6. PMID: 17338148
2. Yi H, Thurberg BL, Curtis S, et al. Characterization of a canine model of glycogen storage disease type IIIa. Dis Model Mech 2012;5(6):804-11. PMID: 22736456
3. OMIA:001577-9615 (AGL). https://omia.org/OMIA001577/9615/