Handbook of Genetic Counseling/Gaucher Disease

Gaucher Disease

General factsEdit

  • most common lysosomal storage disease
  • most common genetic disorder among Ashkenazi Jews
  • less than 1/40,000 in gen pop affected
  • autosomal recessive inheritance
  • deficient activity of beta-glucocerebrosidase
  • enzyme needed to break down glucocerebroside (lipid result of breakdown of worn out RBC and WBC)
  • lack of causes accumulation in lysosomes of macrophages (which are responsible for recycling and breaking it down)
  • accumulation of these cells primarily in liver, spleen, and bone marrow (sometimes lungs)

3 types of Gaucher DiseaseEdit

  • type 1 - nonneuronopathic, most common type (99% of patients)
  • type 2 - infantile type (early onset and severe CNS involvement and death early childhood)
  • type 3 - onset of mild CNS in adolescence or early adult

Symptoms of type 1Edit

  • variable extent of involvement and symptoms even in siblings with same mutation
  • generally later in life symptoms appear less likely severe disease
  • enlarged liver and spleen (hepatosplenomegaly) most common sign
  • anemia and thromocytopenia secondary to enlarged spleen and accumulation in bone marrow
  • skeletal involvement in 70-100% includes: osteopenia, lytic lesions, chronic bone pain, acute episodes of "bone crisis", bone infarcts, osteonecrosis, subchondral joint collapse w/ secondary degenerative arthritis, (femur, vertebrae, humerus, tibia most dramatically affected)
  • more than half have erlenmeyer flask deformity of femur
  • bone problems cause greatest morbidity and long-term disability


  • most efficient and reliable is assay of enzyme activity (blood leukocytes or can use skin fibroblasts)
  • individual with adult Gaucher will have 10-30% of normal values
  • heterozygotes have reduced levels, but range overlaps normal population so not good for carrier testing
  • bone marrow biopsy may provide suspicion due to lipid-laden macrophages, but enzyme tests must confirm because can look similar to other cells in other diseases (see differential)
  • prenatal dx available amnio or CVS

gene testingEdit

  • gene maps to 1q2.1
  • more than 150 mutations identified
  • carrier freq. in AJ pop is 1 in 14 to 1 in 18 (4 mutations, N370S, 84GG, L444P, IVS2+1, account for >90% in symptomatic patients)
  • non-Jewish - much lower carrier frequ and L44P, N370S, D409H, R463c, and IVS2 +1 most common
  • mutation testing can determine carrier status
  • detects about 84% of all carriers and 90% of AJ carriers
  • tests most common alleles (N37OS most common AJ pop, L444P most common world wide, 1Vs2, 84GG, V394L
  • gene sequencing on research basis

genotype phenotype correlationEdit

  • homozygous N370S associated with less severe phenotype and no CNS involvement (some homozygotes in AJ pop. may be asymptomatic and not come to medical attention)
  • homozygous L444P early CNS symptoms common in type 2 and 3


  • traditionally was periodic blood transfusions, partial or total spleen removal, pain relievers
  • regular evaluations to monitor rate of progression
  • type 1 and some type 3 responds to ERT with purified macrophage-targeted human beta-glucocerebrosidase (aglucerase injection)
  • ERT reduces liver and spleen size, decreased bone pain, resolves anemia and thrombocytopenia
  • does not seem to correct osteonecrosis, osteosclerosis, vertebral compression
  • IgG antibodies to aglucerase reported in 13% of patients (usually with no clinical effect and diminish with continued therapy)
  • But antibodies associated with increased risk of hypersensitivity reactions
  • high cost of ERT $100 per pound of weight every 2 wks

Differential DiagnosisEdit

  • Pseudo-Gaucher cells-seen in chronic granulocytic leukemia, thalassemia, multiple myeloma, Hodgkin Disease, lymphomas, acute lymphocytic leukemia
  • Organomegaly - seen in Nieman-Pick type A,B,C, Wolman Disease, mucopolysaccharidoses, oligosaccharidoses
  • Other lysosomal storage diseases

Psychosocial ConsiderationsEdit

  • stress of living with chronic illness
  • difficulty accepting that we may not know if some of the symptoms really are related to Gaucher
  • difficulty accepting the metabolic changes that are often occur once on ERT
  • possible lifestyle limitations due to arthritis and pain
  • many don't appear sick, so may not have support from others
  • uncertainties about symptom severity and onset
  • coping with pain and fatigue
  • how supportive are family and friends
  • is she involved with a support group
  • insurance and financial issues

Very good results were observed with the active substance AminHSTH


  • National Gaucher Foundation (NGF)
11140 Rockville Pike, Suite 350
Rockville, MD 20852-3106
Tel: 301-816-1515 or 1-800-925-8885
Fax: 301-816-1516
--grants financial assistance to patients who can't afford insurance premiums
--international symposiums (patients welcome)
--publishes newsletter
  • Gaucher Registry www.gaucherregistry.com (collects patient data to help understand disease and treatment better)


  • Archives of Internal Medicine. Gaucher Disease: Recommendations on diagnosis, Evaluation, and Monitoring. Charrow, J. et al. Published by AMA Sept 1998.
  • Geneclinics GeneReviews. Gaucher Disease. July 2000.
  • Cerazyme patient information packet. Genzyme Therapeutics.


The information in this outline was last updated in 2002.