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A child with hepatomegaly has fasting hypoglycemia similar to GSD1 but responds to glucagon and has elevated CK due to myopathy.

AR; AGL (glycogen debranching enzyme)

  • Hepatomegaly, hypoglycemia (milder than GSD1)
  • Responds to glucagon (unlike GSD1)
  • Myopathy, cardiomyopathy
  • Elevated CK
  • Liver disease improves with age
  • Not on RUSP; suspected from hepatomegaly with ketotic fasting hypoglycemia plus elevated CK
  • Elevated transaminases, CK; ketotic hypoglycemia (contrast with GSD1: no lactic acidosis, normal/low uric acid)
  • Confirmation: biallelic AGL variants (largely supplanted enzyme/biopsy testing); abnormal limit dextrins on glycogen analysis if tissue obtained
  • Frequent feeding with cornstarch to prevent hypoglycemia
  • High-protein diet (supports gluconeogenesis; supplies muscle substrate)
  • Cardiac and hepatic surveillance (cardiomyopathy, rare cirrhosis/adenomas)

"III" looks like tree branches: GSD III is the debranching enzyme deficiency. Think of a coral reef with branches. Also, 3 x 2 = 6 (alpha-1,6-glucosidase).

Milder von Gierke: GSD III is a milder version with hepatomegaly + hypoglycemia (like GSD1), but gluconeogenesis is intact, so no lactic acidosis. Has myopathy (unlike GSD1, which has no time to develop muscle issues).

Limit dextrins accumulate: the debranching enzyme removes 1,6-linked glucose residues. Without it, branched glycogen fragments (limit dextrins) build up.

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