Table 2.

Disorders to Consider in the Differential Diagnosis of Glycogen Storage Disease Type VI

DisorderGene(s)MOIFeatures of Differential Diagnosis Disorder
Overlapping w/GSD VIDistinguishing from GSD VI
Phosphorylase kinase deficiency (GSD IX) PHKA2
PHKB
PHKG2 		XL
AR
  • Hepatomegaly
  • Fasting ketosis
  • Hypoglycemia
  • ↑ AST/ALT
  • ↑ lipids
  • Male predominance
  • AST & ALT commonly more severely ↑
Hepatic glycogen synthase deficiency (GSD 0)
(OMIM 240600)		 GYS2 AR
  • Fasting hypoglycemia
  • Ketosis
  • Absence of hepatomegaly
  • Postprandial hyperglycemia & hyperlactatemia
Glucose-6-phosphatase deficiency (GSD Ia) G6PC1 AR
  • Hepatomegaly
  • Fasting hypoglycemia
  • ↑ AST/ALT
  • Hyperlipidemia
  • Severe fasting lactic acidosis
  • Hyperuricemia
  • Marked hyperlipidemia
Glucose-6-phosphate transporter deficiency (GSD Ib) SLC37A4 AR
  • Hepatomegaly
  • Fasting hypoglycemia
  • ↑ AST/ALT
  • Hyperlipidemia
  • Neutropenia
  • Crohn disease
  • Hyperuricemia
Debranching enzyme deficiency (GSD III) AGL AR
  • Hepatomegaly
  • Fasting hypoglycemia
  • ↑ AST/ALT
  • Hyperlipidemia
  • Low prealbumin
  • AST & ALT usually markedly ↑
  • Muscle involvement w/↑ CK
Branching enzyme deficiency (GSD IV) GBE1 AR
  • Hepatomegaly
  • ↑ AST/ALT
  • ↓ prealbumin
Lack of hypoglycemia until end-stage liver disease
GLUT2 deficiency (Fanconi-Bickel syndrome; GSD XI) (OMIM 227810) SLC2A2 AR
  • Hepatomegaly
  • Fasting hypoglycemia
  • Fasting ketosis
  • ↑ AST/ALT
  • Low prealbumin
  • Postprandial hyperglycemia
  • Chronic diarrhea
  • Hypophosphatemic rickets
  • Fanconi nephropathy
Fructose-1,6-bisphosphatase deficiency 1 FBP1 AR
  • Hepatomegaly
  • Fasting hypoglycemia
  • ↑ AST/ALT
Fasting hyperlactatemia
Alpha-1 antitrypsin deficiency-related hepatitis 2 SERPINA1 AR
  • Hepatomegaly
  • ↑ AST/ALT
Lack of fasting hypoglycemia & ketosis
Glycerol kinase deficiency (OMIM 307030) GK XLHypoglycemiaKetoacidosis & extremely ↑ glycerol
PRKAG2 deficiency (See Hypertrophic Cardiomyopathy Overview.) PRKAG2 AD
  • Nonlysosomal glycogen accumulation primarily in skeletal & cardiac muscle
  • Ventricular pre-excitation & mild-to-severe cardiac hypertrophy
  • No hypoglycemia
Niemann-Pick disease type B 3 (See ASM Deficiency.) SMPD1 AR
  • Hepatomegaly
  • Growth failure
  • Hyperlipidemia
  • No fasting hypoglycemia
  • Significant splenomegaly
  • Bone & pulmonary involvement
Gaucher disease 3GBA1 (GBA)

AD = autosomal dominant; AR = autosomal recessive; ASM = acid sphingomyelinase; 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; other should also be considered.

2.

Alpha-1 antitrypsin deficiency-related hepatitis is one example of a primary liver disease; other primary liver diseases should also be considered.

3.

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 VI

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