Table 4.

Main characteristics of the different naturally-occurring GSD models.

GSD Type	Natural Occurring	Mutation	Enzyme Activity	Biochemical and Clinical Features	Glycogen Accumulation	Life Expectancy	References
GSD-I	Maltese canine model	G6pc p.121 M>I	G6P Levels reduced	Hypoglycemia, hepatomegaly and necropsy. Failure to thrive, liver and Kidney pale.	Hepatocytes and kidneys	5–8 weeks	[109,110,111,112,113,114,115,116]
GSD-II Pompe	Shorthorn cattle	Gaa c.2454_2455delCA	Loss GAA ativity	Muscle weakness, respiratory distress, congestive heart failure.	Skeletal muscle, heart, and central nervous tissue	12 months	[136,137]
	Brahman cattle	c.1057_1058delTA	Loss GAA ativity	Progressive muscular weakness	Cytoplasmic vacuolation in brain, spinal cord, skeletal muscle, myocardium and Purkinje fibers	12 months	[138,139,140,141]
	Lapphund dogs	Gaa c.2237G>A p.W746X	Absence GAA activity	Megaesophagus, exercise intolerance, and recurrent emesis.	Vacuoles in heart, skeletal muscle, and smooth muscle	10–18 months	[141,142,143,144,145]
	Japanese quails	Defect in GAA protein maturation and processing	Absence GAA activity	Progressive muscle weakness and myopathy	Vacuoles and glycogen depots in muscle and cardiac tissue. Pectoralis most affected tissue.	18 months	[187,188,189,190]
GSD-III Cori	Curly-coated retrievers (CCR)	Gaa c.4223delA	GDE Levels reduced	Progressive muscle damage and hepatomegaly, precense of nudles, cirrhosis. High ALT, AST and ALP levels, slightly high CPK levels.	Cardiomyocytes, gradual increase in Liver and skeletal muscle	11–12 years	[191,192,193]
GSD-IV Andersen	American Quarter Horse foals (AQHs)	Gbe1 p.Y34X	GBE amount and activity reduced	Stillbirth, transient flexural limb deformities, respiratory or cardiac failure.	Skeletal muscle, liver and central nervous system	1–18 weeks	[197]
	Norwegian forest cats	Gbe1 g. IVS11 + 1552_IVS12-1339 del6.2 kb ins334 bp	Absence GBE activity	Skeletal muscle atrophy, progressive neurological decline, generalized muscle tremors.	Skeletal muscle, Liver, cardiatic muscle, neurvous system	1–13 months	[198]
GSD-V McArdle	Charolais cattle	Pygm p.W489R	GP-MM amount and activity reduced	Exercise intolerance, rhabdomyolysis, high CK levels and myoglobinuria.	Skeletal Muscle	Not reported	[202,203]
	Merino sheep	missense mutation in the 3′ splice acceptor site of intron 19 of Pygm	Absence GP-MM activity	Exercise intolerance, rhabdomyolysis	Skeletal Muscle	Not reported	[204,205,206,207]
GSD-VII Tarui	English Springer Spaniel	Pfkm c.2228 G>A	Absence of PFKM activity	Chronic hemolytic anemia, hemolytic crises, hemoglobinuria, hyperbilirubinuria, moderately increased serum creatine kinase activity, muscle wasting.	Skeletal muscle	11 years	[217,218,219,220,221,222,223,224]
	American Cocker Spaniels	Pfkm c.2228 G>A	Absence of PFKM activity		Skeletal muscle	11 years	[217,218,219,220,221,222,223,224]
	Whippet	Pfkm c.2228 G>A	Absence of PFKM activity	Mimics English Springer Spaniel symptoms but present cardicac and muscular abnormalities	Skeletal muscle	4 years	[217,218,219,220,221,222,223,224]
	Wachtelhunds	Pfkm c.550C>T	PFKM activity reduced	Exercise intolerance, hemolytic anemia, pigmenturia	Skeletal muscle	4 years	[225,226]