Liver & intrahepatic bile ducts
Metabolic diseases
Gaucher disease
Author: Komal Arora, M.D.
Topic Completed: 1 April 2012
Minor changes: 15 December 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Liver[MH] Gaucher disease[TI]
Table of Contents
Definition / general | Epidemiology | Etiology | Clinical features | Diagnosis | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Electron microscopy description | Electron microscopy images | Differential diagnosis | Additional referencesCite this page: Arora K. Gaucher disease. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livergauchers.html. Accessed April 12th, 2021.
Definition / general
- Preferable to "Gaucher's disease"
Epidemiology
- Highest risk in Ashkenazi Jews; 1 in 15 are carriers
Etiology
- 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)
Clinical features
- Three subtypes; all may have hepatosplenomegaly, hypersplenism, osteoporosis, yellow brown skin, anemia (GeneReviews: Gaucher Disease [Accessed 26 October 2017])
- Type I: nonneuropathic, 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
- < 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
- 51 year old man with chronic liver disease (Case of the Week #164)
Treatment
- 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)
Microscopic (histologic) description
- Enlarged Kupffer cells and portal macrophages with "crinkled paper" cytoplasm
Microscopic (histologic) images
Contributed by Komal Arora, M.D.
Various images
PAS
Iron
Thick section
Electron microscopy description
- Intralysosomal tubular inclusions
- Angulated lysosomes
Electron microscopy images
Case #164
Electron microscopy
Differential diagnosis
- Gaucher-like cells also seen in CML, AML and CLL
- Niemann-Pick disease: foamy and vacuolated cytoplasm due to sphinomyelin accumulation
- Pompe disease: primarily affects skeletal and cardiac muscle
