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Gaucher's disease
Familial disorder resulting from glucocerebrosidase deficiency.
Epidemiology:
1) gene frequency in Ashkenazi Jews is ~6.8%
2) incidence 1/850 in Ashkenazi Jews [4]
3) considered rare
Pathology:
1) glucocerebrosidase deficiency
2) deposition of glucosylceramides in monocytes & macrophages
3) accumlation of glucosylceramide-laden macrophages (Gaucher cells) in spleen, liver, bone marrow & brain
4) inflammatory features [4]
Genetics:
1) autosomal recessive
2) defects in PSAP saposin C region are a cause of Gaucher disease variant
Clinical manifestations:
1) abdominal distension with hepatosplenomegaly
2) painful bone lesions
3) erosion of long bones & the pelvis
4) brown pigmentation of conjunctiva
5) brown to yellow skin
6) mental retardation in infantile form only
7) abnormal eye movement associated with neuronopathic forms (types 2,3)
Laboratory:
1) complete blood count (CBC)
a) anemia
b) leukopenia
c) thrombocytopenia
2) enzyme deficiency of cultured leukocytes or fibroblasts
3) bone marrow biopsy: Gaucher cells
4) carrier status must be determined by RT-PCR*
- GBA gene mutation
5) see ARUP consult [5]
* reverse transcriptase polymerase chain reaction
Radiology:
1) localized thinning of bony cortex
2) erosion & compression of femoral head
Complications:
1) aseptic necrosis of the femoral head
2) vertebral collapse
3) increased frequency of multiple myeloma
Management:
1) alglucerase (Ceredase), enzyme replacement (expensive)
a) may reduce hepatosplenomegaly
b) may improve hematopoietic function
c) generally reserved for patients with severe disease
2) substrate reduction therapy (Zavesca)
3) hemisplenectomy
4) allogeneic bone marrow transplantation
Related
Gaucher cell
glucocerebroside (glucosylceramide)
glucosylceramidase; lysosomal acid glucosylceramidase; acidic beta glucosidase; beta-glucocerebrosidase (GBA1, GBA, GC, GLUC)
Specific
Gaucher's disease type 1 (juvenile)
Gaucher's disease type 2 (infantile)
Gaucher's disease type 3 (juvenile & adult)
General
sphingolipidosis; sphingolipodystrophy; cerebral lipidosis
Properties
ACCUMULATION: glucocerebroside
DEFICIENCY: glucosylceramidase
Database Correlations
OMIM correlations
MORBIDMAP 176801
References
- Textbook of Biochemistry with Clinical Correlations,
3rd ed., TM Devlin (ed), Wiley-Liss, NY 1992 pg 459
- Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed)
Lippincott-Raven, Philadelphia, 1998, pg 451
- Medical Knowledge Self Assessment Program (MKSAP) 11, American
College of Physicians, Philadelphia 1998
- Zimmerman, Ari
- ARUP Consult: Gaucher Disease
https://arupconsult.com/ati/gaucher-disease
- ARUP Consult: Jewish Genetic Disease
The Physician's Guide to Laboratory Test Selection & Interpretation
- Ashkenazi Jewish Genetic Diseases Carrier Screening Algorithm
https://arupconsult.com/algorithm/jewish-genetic-diseases-carrier-screening-algorithm
- Ashkenazi Jewish Genetic Diseases Panel
https://arupconsult.com/ati/ashkenazi-jewish-genetic-diseases-panel