Test Detail

Hepatorenal glycogenosis due to glucose-6-phosphatase deficiency, the enzyme that releases glucose from glucose-6-phosphate. It causes fasting hypoglycaemia, glycogen accumulation in the liver and kidney, massive hepatomegaly and lactic acidosis, with failure to thrive and risk of coma and death in the first months. It is inherited in an autosomal recessive manner and is associated with mutations in the G6PC gene, which differ according to breed.

Affected breeds: Maltese (M121I variant, first breed described) and German Pinscher (insertion in exon 5; carrier frequency ~12 % in a cohort of 208 German Pinschers). Rare but severe disease in both breeds.

- Test breeding animals with the G6PC test specific to their breed\n- Do not mate two carriers: 25 % risk of affected homozygotes, with early lethality\n- A carrier may be mated to a clear animal; offspring intended for breeding must be tested\n- In the German Pinscher, given the reported carrier frequency, systematic screening before breeding is advisable\n- Exclude affected animals from breeding and test the parents and siblings of cases

Differential diagnosis with other glycogenoses (GSD II/Pompe, GSD IIIa), congenital liver diseases and causes of neonatal/juvenile hypoglycaemia (portosystemic, hypopituitarism). Clinical management involves avoiding fasting (frequent feeding, raw cornstarch) and correcting the acidosis; the prognosis without treatment is poor. Confirmation is molecular and allows familial genetic counselling.

1. Kishnani PS et al. (1997) Isolation and nucleotide sequence of canine glucose-6-phosphatase mRNA: identification of mutation in puppies with glycogen storage disease type Ia. Biochem Mol Med 61:168-177. PMID: 9259982
2. Christen M et al. (2021) Polyadenine insertion disrupting the G6PC1 gene in German Pinschers with glycogen storage disease type Ia (GSD1A). Anim Genet 52:900-902. PMID: 34610166
3. OMIA:000418-9615 — Glycogen storage disease Ia in Canis lupus familiaris (dog).