描述
Gaucher disease is caused by a defect in the GBA gene which codes for glucosylceramidase. A defect in this enzyme results in accumulation of glucosylceramide in in brain, bone marrow, liver, spleen, lungs, and other organs. Gaucher’s disease has three common clinical subtypes. Type I (or non-neuropathic type) is the most common form of the disease. Symptoms may begin early in life or in adulthood. They include enlarged liver, grossly enlarged spleen, skeletal weakness and bone disease. Spleen enlargement and bone marrow replacement cause anemia, thrombocytopenia and leukopenia. Type II (or acute infantile neuropathic Gaucher’s disease) typically begins within 6 months of birth. Symptoms include an enlarged liver and spleen, extensive and progressive brain damage, eye movement disorders, spasticity, seizures, limb rigidity, and a poor ability to suck and swallow. Affected children usually die by age 2. Type III (the chronic neuropathic form) can begin at any time in childhood or even in adulthood. Major symptoms include an enlarged spleen and/or liver, seizures, poor coordination, skeletal irregularities, eye movement disorders, blood disorders including anemia and respiratory problems. Patients often live into their early teen years and adulthood. For type 1 and most type 3 patients, enzyme replacement treatment with intravenous recombinant glucocerebrosidase (imiglucerase) can dramatically decrease liver and spleen size, reduce skeletal abnormalities, and reverse other manifestations. Successful bone marrow transplantation cures the non-neurological manifestations of the disease. Surgery to remove the spleen (splenectomy) may be required on rare occasions if the patient is anemic or when the enlarged organ affects the patient’s comfort. Blood transfusion may benefit some anemic patients. Other patients may require joint replacement surgery to improve mobility and quality of life. Other treatment options include antibiotics for infections, antiepileptics for seizures, bisphosphonates for bone lesions, and liver transplants. Substrate reduction therapy may prove to be effective in stopping Type 2, as it can cross through the blood barrier into the brain. There is currently no effective treatment for the severe brain damage that may occur in patients with types 2 and 3 Gaucher disease.