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Updated: Jun 16 2021

Gaucher Disease

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  • summary
    • Gaucher Disease is a congenital lysosomal storage disorder caused by an autosomal recessive mutation in B-glucocerebrosidase. Patients present with hematological abnormalities, joint pain, osteonecrosis, and developmental delay. 
    • Diagnosis is made by elevated plasma levels of glucocerebrosides.
    • Treatment involves a multidisciplinary approach to address orthopedic manifestations, hematologic abnormalities, and neurological abnormalities.
  • Epidemiology
    • Incidence
      • most common lysosomal storage disase
      • incidence of ~1 in 40,000 people in general population
    • Demographics
      • more common in Ashkenazi Jewish origin
  • Etiology
    • Mechanism
      • deficiency in B-glucocerebrosidase
    • Pathophysiology
      • cell biology
        • enzyme deficency leads to disturbances in cell metabolism with accumulation of sphingolipids in the
          • liver
          • spleen
          • bone marrow
    • Genetics
      • inheritance pattern
        • autosomal recessive
      • classification
        • Type 1 (B-glucocerebrosidase deficency) is most common
        • Type 2
        • Type 3 (with CNS involvement)
  • Classification
      • Gaucher Classification
      • Type
      • Clinical Features
      • Prognosis
      • Type 1
      • (Adult Type)
      • Easy bruising
      • Anemia, fractures
      • Treatable with enzyme replacement therapy (fatal if enzyme substitute is not given)
      • Type 2
      • (InfantileType)
      • Lethal by age 3
      • Brain and organ involvement
      • Untreatable and lethal during infancy
      • Type 3
      • (JuvenileType)
      • Onset in teen years
      • Thrombocytopenia, anemia, enlarged liver
      • Fractures
      • Gradual brain involvement
      • Type 3 is clinically diverse.
      • The non-CNS effects respond well to enzyme replacement therapy
  • Presentation
    • Symptoms (will depend on the type of Gaucher's disease)
      • Systemic Manifestations
        • fatigue (anemia)
        • prolonged bleeding (thrombocytopenia)
        • fever, chills, sweats (infection)
        • seizure, developmental delay (CNS involvement)
      • Orthopaedic Manifestations
        • bone pain (fracture, osteomyelitis)
        • joint pain or contracture
        • bone crisis (osteonecrosis)
    • Physical exam
      • inspection
        • abnormal skin and bruising
      • palpation
        • hepatosplenomegaly
      • auscultation
        • cardiac mumur
      • musculoskeletal
        • bone deformities (80% of patients with Gaucher will develop deformities of the distal femur or proximal tibia)
        • joint contractures
        • pathologic fractures
  • Evaluation
    • Labs
      • Full blood count
        • anemia and thrombocytopenia are common
      • diagnosis confirmed by elevated plasma levels of glucocerebrosides
    • Histology
      • bone marrow aspirate shows a giant binucleate storage cell filled with glucocerebrosides
        • which accumulate because of an hereditary deficiency of Beta-glucocerebrosidase
    • Imaging
      • radiographs
        • chest
          • may reveal cardiac involvement (e.g. cardiac enlargement, etc)
        • skeletal
          • may reveal pathologic fractures, osteonecrosis, abnormal bone remodeling or joint deformity
            • "erlenmeyer flask" appearance of distal femur and proximal tibia
          • almost all patients have diffuse osteopenia
      • CT/MRI
        • visceral
          • abdomen may reveal organomegaly
        • skeletal
          • increased prevalence of osteomyelitis in patients with Gaucher's disease
          • chronic vascular insults may lead to osteonecrosis in the proximal and distal femur, proximal tibia and proximal humerus most commonly
  • Treatment
    • Nonoperative
      • observation and supportive therapy
        • indications
          • unaffected patients (e.g., no blood result irregularities, minimal organ enlargement, no bony lesions on MRI)
        • modalities
          • extended multidisciplinary approach is essential
      • enzyme replacement therapy
        • indications
          • all children and symptomatic patients
          • not effective in Type 2 Gaucher's disease
        • modalities
          • imiglucerase
          • velaglucerase alfa
          • taliglucerase alfa
      • substrate reduction therapy
        • indications
          • less severely affected patients that cannot tolerate IV replacement therapy
        • modalities
          • miglustat
    • Operative
      • bone marrow transplant
        • if performed early may be curative
  • Complications
    • Fracture management
      • preoperative optimization with enzyme therapy is critical
      • availability of additional blood, clotting factors and platelets due to increased bleeding risk
      • anesthisologist to maintain oxygenation to avoid precipitating bone crisis
      • increased risk of infection
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