Liver and intrahepatic bile ducts - nontumor
Metabolic diseases
Glycogen storage disease

Author: Komal Arora, M.D. (see Authors page)

Revised: 27 October 2017, last major update April 2012

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Glycogen storage diseases[TI]

Cite this page: Arora, K. Glycogen storage disease. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/liverglycogenstoragedisease.html. Accessed November 22nd, 2017.
Definition / general
  • Called GSD, also glycogenosis and dextrinosis
  • Due to defects in glycogen synthesis or breakdown within muscles, liver, other cell types; either genetic or acquired (Wikipedia: Glycogen Storage Disease [Accessed 27 October 2017])
  • Estimated to occur in 1 per 20,000 - 25,000 births in US; 1 per 40,000 births elsewhere
  • ~ 11 distinct types
Type I
Definition / general
  • Also known as von Gierke disease or hepatorenal glycogenosis
  • Type Ia: glucose-6-phosphatase (G6Pase) deficiency
  • Type Ib: translocase T1 deficiency
  • Type Ic: translocase T2 deficiency (carries inorganic phosphates from microsomes into cytosol and pyrophosphates from cytosol into microsomes)
  • Type Id: deficiency in transporter that translocates free glucose molecules from microsomes into cytosol (eMedicine: Glycogen Storage Diseases Types I - VII [Accessed 27 October 2017])


Microscopic (histologic) description
  • Mosaic pattern due to enlarged hepatocytes compressing sinusoids
  • Fatty change, hyperglycogenated nuclei


Microscopic (histologic) images

Images hosted on other servers:

Swollen hepatocytes
in a mosaic pattern
with compression
of sinusoids



Electron microscopy description
  • Increased cytoplasmic glycogen, lipid droplets, glycogenated nuclei
Type Ia
Definition / general
  • Rare; due to absence of glucose-6-phosphatase, required for gluconeogenesis and glycogenolysis
  • Symptoms: hypoglycemia and marked hepatomegaly in first year of life; later short stature, chronic lactic acidosis, focal segmental glomerulosclerosis, hepatic adenomas, iron deficiency


Diagnosis
  • Deficient G6Pase activity in fresh and frozen liver tissue


Case reports

Treatment

Gross description
  • Enlarged, pale liver
  • May have variable sized tumor nodules


Microscopic (histologic) description
  • Large hepatocytes with prominent cell membrane and glycogenated nuclei
  • PAS+ accumulated glycogen
  • Rarely contains Mallory hyaline and steatosis in hepatic adenomas


Microscopic (histologic) images

Images hosted on other servers:

Adenomas

Adenomas with steatosis and Mallory hyaline

Type Ib
Definition / general
  • Enzyme levels are normal but transmembrane transport protein translocase 1 is ineffective (Orphanet J Rare Dis 2011;6:27)
  • Normal G6Pase activity in frozen tissue and lowered activity in fresh specimens
  • Altered neutrophil functions predisposes to gram positive bacterial infections
Type II
Definition / general
  • Also called Pompe disease
  • Deficiency of lysosomal acid α-glucosidase, causes massive lysosomal glycogen accumulation in cardiac and skeletal muscles (Wikipedia: Glycogen Storage Disease Type II [Accessed 27 October 2017])
  • Infantile form: severe hypotonia associated with hypertrophic cardiomyopathy; death from heart and respiratory failure may occur during the first year of life
  • Late onset form: progressive muscle weakness


Treatment
  • Enzyme replacement therapy with recombinant human lysosomal hydrolase acid α-glucosidase (cost $300,000 per year), plus supportive and physical therapies (Curr Pharm Biotechnol 2011;12:902)


Microscopic (histologic) description
  • Increased hepatocellular glycogen


Electron microscopy description
  • Intralysosomal glycogen
Type III
Definition / general

Microscopic (histologic) description
  • Mosaic pattern due to enlarged hepatocytes compressing sinusoids
  • Fatty change, hyperglycogenated nuclei


Microscopic (histologic) images

Images hosted on other servers:

Hypertrophic hepatocytes
with pale staining
cytoplasm and
portal fibrosis



Electron microscopy description
  • Increased cytoplasmic glycogen, lipid droplets, glycogenated nuclei
Type IV
Definition / general
  • Also called amylopectinosis, Andersen disease, adult polyglucosan body disease
  • Rare, autosomal recessive, caused by deficiency of glycogen branching enzyme on 3p14, leading to excessive deposition of structurally abnormal, amylopectin-like glycogen in affected tissues, causing irreversible tissue and organ damage (J Inherit Metab Dis 2010;33:S83)
  • Classic form: progressive hepatic fibrosis through age 18 months causing hepatosplenomegaly, failure to thrive, death by 5 years
  • Rare nonprogressive form: no cirrhosis, live to adulthood; adult onset progressive neurogenic bladder, gait difficulties (i.e. spasticity and weakness) from mixed upper and lower motor neuron involvement, sensory loss predominantly in the distal lower extremities and mild cognitive difficulties (GeneReviews: Adult Polyglucosan Body Disease [Accessed 27 October 2017])
  • Neuromuscular form: severe hypotonia at birth causing death or myopathy in late childhood or nervous system dysfunction as adults


Diagnosis
  • Amylopectin-like material in tissue


Case reports

Treatment
  • Liver transplantation


Microscopic (histologic) description
  • Basophilic intracytoplasmic inclusions, PAS+, diastase partially resistant


Microscopic (histologic) images

Images hosted on other servers:

H&E (inclusions), PAS, colloidal iron, EM

Cytoplasmic inclusions in hepatocytes



Electron microscopy description
  • Filamentous nonbranching cytoplasmic aggregates


Differential diagnosis
  • Lafora disease: similar inclusions but not coarsely clumped, older age with epilepsy, myoclonus, dementia