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 login to view 3 more bullets 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 login to view 1 more bullet skeletal login to view 3 more bullets CT/MRI visceral login to view 1 more bullet skeletal login to view 2 more bullets Treatment Nonoperative observation and supportive therapy indications login to view 1 more bullet modalities login to view 1 more bullet enzyme replacement therapy indications login to view 2 more bullets modalities login to view 3 more bullets substrate reduction therapy indications login to view 1 more bullet modalities login to view 1 more bullet 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