Table 2.

Disorders in the Differential Diagnosis of Glycogen Storage Disease Type I

GeneDiffDx DisorderMOIFeatures of DiffDx Disorder
Overlapping w/GSD IDistinguishing from GSD I
AGL Debranching enzyme deficiency (GSD III)AR
  • Hepatomegaly
  • Fasting hypoglycemia
  • ↑ AST/ALT
  • Hyperlipidemia
  • AST & ALT usually markedly ↑
  • Muscle involvement w/↑ CK
  • Normal uric acid, lactate
FBP1 Fructose-1,6-bisphosphatase deficiency 1AR
  • Hepatomegaly
  • Fasting hypoglycemia
  • ↑ AST/ALT
Fasting hyperlactatemia
GBA1 (GBA)Gaucher disease 2AR
  • Hepatomegaly
  • Growth failure
  • Hyperlipidemia
  • Pulmonary hypertension (rare)
  • Bone disease / osteoporosis
  • No fasting hypoglycemia
  • Significant splenomegaly
  • Bone infarcts, AVN of femoral head & pulmonary involvement in the form of pulmonary infiltrates
GBE1 Branching enzyme deficiency (See GSD IV.)AR
  • Hepatomegaly
  • ↑ AST/ALT
  • Lack of hypoglycemia until end-stage liver disease
  • Liver cirrhosis
GK Glycerol kinase deficiency (OMIM 307030)XLHypoglycemiaKetoacidosis & extremely ↑ glycerol
GYS2 Hepatic glycogen synthase deficiency (GSD 0) (OMIM 240600)AR
  • Fasting hypoglycemia
  • Ketosis
  • Absence of hepatomegaly
  • Postprandial hyperglycemia & hyperlactatemia
PHKA2
PHKB
PHKG2 		Liver phosphorylase kinase deficiency (GSD IX)XL
AR
  • Hepatomegaly
  • Fasting ketosis
  • Hypoglycemia
  • ↑ AST/ALT
  • ↑ lipids
  • Male predominance
  • AST & ALT commonly more severely ↑
  • Liver fibrosis
SLC2A2 GLUT2 deficiency (Fanconi-Bickel syndrome; GSD XI) (OMIM 227810)AR
  • Hepatomegaly
  • Fasting hypoglycemia
  • Fasting ketosis
  • ↑ AST/ALT
  • Postprandial hyperglycemia
  • Chronic diarrhea
  • Hypophosphatemic rickets
  • Fanconi nephropathy
  • Significant short stature
SMPD1 Chronic visceral ASMD (Niemann-Pick disease type B) 2 (See ASM Deficiency.)AR
  • Hepatomegaly
  • Growth failure
  • Hyperlipidemia
  • Bone & pulmonary involvement
  • No fasting hypoglycemia
  • Significant splenomegaly

AD = autosomal dominant; ALT = alanine aminotransferase; AR = autosomal recessive; ASMD = acid sphingomyelinase deficiency; AST = aspartate aminotransferase; AVN = avascular necrosis; CK = creatine kinase; GSD = glycogen storage disease; MOI = mode of inheritance; XL = X-linked

1.

Fructose-1,6-bisphosphatase deficiency is one example of a disorder of gluconeogenesis; others should also be considered.

2.

Niemann-Pick disease type B and Gaucher disease are examples of metabolic storage disorders; other metabolic storage disorders should also be considered.

From: Glycogen Storage Disease Type I

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