Liver & intrahepatic bile ducts
Metabolic diseases
Glycogen storage diseases
Author: Komal Arora, M.D.
Topic Completed: 1 April 2012
Minor changes: 20 January 2020
Copyright: 2002-2020, PathologyOutlines.com, Inc.
PubMed Search: Glycogen storage diseases[TI]
Cite this page: Arora K. Glycogen storage diseases. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverglycogenstoragedisease.html. Accessed August 7th, 2020.
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
Microscopic (histologic) description
Microscopic (histologic) images
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Electron microscopy description
- 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
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Swollen hepatocytes
in a mosaic pattern
with compression
of sinusoids
Electron microscopy description
- Increased cytoplasmic glycogen, lipid droplets, glycogenated nuclei
Type Ia
Definition / general
Diagnosis
Case reports
Treatment
Gross description
Microscopic (histologic) description
Microscopic (histologic) images
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- 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
Microscopic (histologic) images
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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
Treatment
Microscopic (histologic) description
Electron microscopy description
- 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
Microscopic (histologic) images
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Electron microscopy description
- 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
Diagnosis
Case reports
Treatment
Microscopic (histologic) description
Microscopic (histologic) images
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Electron microscopy description
Differential diagnosis
- 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
- 10 month old boy with massive hepatomegaly (Arch Pathol Lab Med 2002;126:630)
Treatment
- Liver transplantation
Microscopic (histologic) description
- Basophilic intracytoplasmic inclusions, PAS+, diastase partially resistant
Microscopic (histologic) images
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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
