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Liver & intrahepatic bile ducts

Metabolic diseases

Glycogen storage diseases

Author: Komal Arora, M.D.

Last author update: 1 April 2012

Last staff update: 8 July 2022

Copyright: 2002-2022, PathologyOutlines.com, Inc.

PubMed Search: Glycogen storage diseases

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Table of Contents

Cite this page: Arora K. Glycogen storage diseases. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverglycogenstoragedisease.html. Accessed August 17th, 2022.

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

28 year old woman with multiple hepatic adenomas (Arch Pathol Lab Med 2003;127:e402)

Treatment

Liver transplant (Transplant Proc 2011;43:1196)

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

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

Deficiency of debrancher enzyme amylo-1,6-glucosidase due to various mutations causes hypoglycemia (Hum Mol Genet 2009;18:2045)
Also called Cori disease
Variable liver, cardiac muscle and skeletal muscle involvement (GeneReviews: Glycogen Storage Disease Type III [Accessed 27 October 2017])
GSD IIIa: most common subtype (85%), liver and muscle involvement
GSD IIIb: 15%; liver involvement only

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