Gaucher Disease

Key Features

• Caused by a deficiency of β-glucocerebrosidase, leading to an accumulation of sphingolipid within phagocytic cells throughout the body

• Inherited as an autosomal recessive

• Hundreds of mutations have been found

• Most common in people of Ashkenazi Jewish ancestry

• Peripheral neuropathy may develop

• Two uncommon forms of Gaucher disease, types II and III, involve neurologic accumulation of sphingolipid and neurologic problems

• Type II is of infantile onset and has a poor prognosis

Clinical Findings

• Anemia and thrombocytopenia are common and primarily due to hypersplenism, but marrow infiltration with Gaucher cells may be a contributing factor

• Abdomen can become painfully distended from enlargement of the liver and spleen

• Cortical erosions of bones, especially vertebrae and femur, are due to local infarctions

• Bone pain, termed "crises" reminiscent of pain seen in sickle cell disease

Diagnosis

• Bone marrow aspirates reveal typical Gaucher cells, which have an eccentric nucleus and periodic acid-Schiff–positive inclusions, along with wrinkled cytoplasm and inclusion bodies of a fibrillar type

• Serum acid phosphatase elevated

• Deficient glucocerebrosidase activity in leukocytes confirms diagnosis

• Prenatal diagnosis through mutation analysis is feasible

• Because of an increased risk of malignancy, especially multiple myeloma and other hematologic cancers, regular screening of adults may be warranted

Treatment

• Imiglucerase

  • Recombinant form of the enzyme glucocerebrosidase

  • Dosage: 30 units/kg/mo intravenously

  • Reduces total body stores of glycolipid

  • Improves orthopedic and hematologic, but not neurologic, manifestations

• Eliglustat tartrate, an oral inhibitor of glucosylceramide synthase

  • Reduces the compound that accumulates

  • Eliminates the need for frequent intravenous infusions

• Enzyme replacement often obviates the need for splenectomy in adults with thrombocytopenia due to splenic sequestration