Gaucher Disease

Genetics / Hematology

Overview

Definition

An autosomal recessive lysosomal storage disorder characterized by glucocerebrosidase deficiency, leading to glucocerebroside accumulation in macrophage lysosomes.

Epidemiology

The most common lysosomal storage disease, carrier rate 1 in 10 in Ashkenazi Jews.

Etiology & Risk Factors

  • GBA gene mutations
  • Accumulation of lipid-laden Gaucher cells in organs

Clinical Symptoms

  • Hepatosplenomegaly
  • Anemia and thrombocytopenia
  • Bone pain and skeletal crises
  • Easy bruising

Clinical Approach

Diagnosis

  • Reduced glucocerebrosidase enzyme activity in leukocytes
  • Bone marrow showing 'wrinkled tissue paper' macrophages

Management

  • Enzyme Replacement Therapy (ERT: Imiglucerase)
  • Substrate Reduction Therapy (SRT: Miglustat)

Complications

  • Avascular necrosis of bone
  • Severe thrombocytopenia / Hemorrhage
  • Osteoporosis