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Liver and intrahepatic bile ducts-nontumor

Metabolic diseases

Gaucher disease


Reviewers: Komal Arora, M.D. (see Reviewers page)
Revised: 25 April 2012, last major update April 2012
Copyright: (c) 2004-2012, PathologyOutlines.com, Inc.

General
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● Preferable to “Gaucher’s disease”

Etiology
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● Lysosomal storage disease caused by an autosomal recessive mutation in the β glucocerebrosidase gene (also called glucosylceramidase and β glucosidase)
● Defective enzyme leads to accumulation of glucocerebroside substrate in cells of the mononuclear phagocyte system, including histiocytes in the spleen, lymph nodes, bone marrow, GI and GU tracts; Kupffer cells in liver; osteoclasts in bone; microglia in CNS; and alveolar macrophages in lungs (Arch Pathol Lab Med 2008;132:851)

Epidemiology
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● Highest risk in Ashkenazi Jews - 1 in 15 are carriers

Clinical description
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● Three subtypes; all may have hepatosplenomegaly, hypersplenism, osteoporosis, yellow-brown skin, anemia (Gaucher Disease. GeneReviews™ [Internet] 1993-2000 Jul 27 [updated 2011 Jul 21])
● Type I - non-neuropathic, may be mild
● Type II (acute infantile neuropathic Gaucher disease) - affects infants within a few months of birth, usually fatal within 2 years; may have seizures and dementia
● Type III - chronic neurological variant, with onset anytime between birth and adulthood, presents with slowly progressing neurological decline; may have seizures and dementia

Diagnosis
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● <15% of mean normal glucocerebrosidase activity in peripheral blood leukocytes is diagnostic
● Note: enzyme activity in carriers (heterozygotes) is generally half-normal, but may overlap with healthy controls
● Molecular analysis, particular in Ashkenazi patients, may also be helpful

Case reports
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● 51 year old man with chronic liver disease (Case of the Week #164)

Treatment
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● Enzyme replacement therapy with imiglucerase (Cerezyme), a recombinant version of β glucocerebrosidase, for patients with Types I or III (Curr Opin Pediatr 2007;19:628)

Micro description
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● Enlarged Kupffer cells and portal macrophages with “crinkled paper” cytoplasm

Micro images
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Various images


PAS


Iron

Electron microscopy description
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● Intralysosomal tubular inclusions
● Angulated lysosomes

Electron microscopy images
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Thick section


Electron microscopy

Differential diagnosis
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Niemann-Pick disease: foamy and vacuolated cytoplasm due to sphinomyelin accumulation
Pompe disease: primarily affects skeletal and cardiac muscle
● Gaucher-like cells also seen in CML, AML and CLL

Additional references
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eMedicine, Wikipedia, Am J Hematol 2011;86:110

End of Liver and intrahepatic bile ducts-nontumor > Metabolic diseases > Gaucher disease


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