RESUMO
OBJECTIVE: To assess the long-term systemic and neurologic responses to enzyme replacement therapy (ERT) with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease. STUDY DESIGN: Patients with type 3 Gaucher's disease (n = 21), aged 8 months to 35 years, were enrolled in a prospective study. Enzyme dose was adjusted to control systemic manifestations. Clinical and laboratory evaluations were performed at baseline and every 6 to 12 months thereafter. Patients were followed up for 2 to 8 years. RESULTS: Significant improvement in hemoglobin levels, platelet count, and acid phosphatase values occurred. Liver and spleen volume markedly decreased, and bone structure improved. Nineteen patients had asymptomatic interstitial lung disease unresponsive to ERT. Supranuclear gaze palsy remained stable in 19 patients, worsened in one patient, and improved in one. Cognitive function remained unchanged or improved over time in 13 patients but decreased in 8 patients, 3 of whom developed progressive myoclonic encephalopathy accompanied by cranial magnetic resonance imaging and electroencephalographic deterioration. CONCLUSIONS: At relatively high doses, ERT reverses almost all the systemic manifestations in patients with type 3 Gaucher's disease. Most treated patients do not deteriorate neurologically. Novel therapeutic strategies are required to reverse the pulmonary and neuronopathic aspects of the disease.
Assuntos
Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Adolescente , Adulto , Determinação da Idade pelo Esqueleto , Criança , Pré-Escolar , Eletroencefalografia/métodos , Feminino , Doença de Gaucher/sangue , Doença de Gaucher/diagnóstico , Doença de Gaucher/psicologia , Glucosilceramidase/administração & dosagem , Humanos , Testes de Inteligência , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Partial splenectomy was introduced to achieve the benefits of splenectomy and to avoid the risk of overwhelming infection in patients with symptomatic Gaucher disease. We observed regrowth of the splenic remnant, reemergence of preoperative symptoms, and new bone involvement among most of our patients who had undergone partial splenectomy. Enzyme replacement therapy has markedly limited indications for splenectomy, partial or total, for Gaucher disease.
Assuntos
Doença de Gaucher/cirurgia , Esplenectomia , Adolescente , Adulto , Doenças Ósseas/etiologia , Criança , Feminino , Seguimentos , Doença de Gaucher/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteonecrose/etiologia , Baço/crescimento & desenvolvimento , Resultado do TratamentoRESUMO
Long-term studies of a child with Gaucher disease indicated that the response to treatment with macrophage-targeted glucocerebrosidase (glucosylceramidase) is dose dependent, and that the hematologic response precedes the skeletal response.