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