RESUMO
Introducción: La enfermedad de Gaucher es una entidad de acúmulo lisosomal, con un patrón de herencia autosómico recesivo, debido a la deficiencia de le enzima betaglucocerebrosidasa ácida. El gen está mapeado en el cromosoma 1q21 y se han descrito más de 500 mutaciones. Se caracteriza por presentar anemia, trombocitopenia, hepatoesplenomegalia, manifestaciones esqueléticas y, en ocasiones, compromiso neurológico. Entre los tratamientos se utiliza el reemplazo enzimático con imiglucerasa. Objetivo: Evaluar los resultados de la aplicación de imiglucerasa (Cerezyme®) en pacientes con enfermedad de Gaucher. Métodos: Se realiza un estudio longitudinal, descriptivo para evaluar el comportamiento de las variables clínicas, hematológicas y ultrasonográficas de ocho pacientes cubanos con enfermedad de Gaucher tras recibir el tratamiento sustitutivo enzimático. Se evaluaron al año, cinco y de diez a quince años de tratamiento. Resultados: Al inicio, todos los pacientes presentaron anemia y la mayoría tuvieron trombocitopenia y hepatoesplenomegalia al diagnóstico de la enfermedad. Los pacientes con manifestaciones neurológicas y la mutación L444P en estado homocigótico se clasificaron en EG tipo 3, el resto en tipo1. En todos los pacientes se constató aumento de las cifras de hemoglobina, la elevación del número de plaquetas y reducción de la hepatoesplenomegalia posterior al año de tratamiento. Los pacientes con tipo 3 mantuvieron la afectación neurológica. No se reportaron reacciones adversas al medicamento. Conclusiones: La terapia de reemplazo enzimática con imiglucerasa (Cerezyme®) es un pilar fundamental en el tratamiento de los pacientes con esta enfermedad, lo cual influye de forma positiva en la calidad de vida, obteniéndose mejores resultados con su comienzo en edad pediátrica.
Introduction: Gaucher disease is an entity of lysosomal accumulation, with an autosomal recessive inheritance pattern, due to the deficiency of the acid betaglucocerebrosidase enzyme. The gene is mapped on chromosome 1q21 and more than 500 mutations have been described. It is characterized by anemia, thrombocytopenia, hepatosplenomegaly, skeletal manifestations and sometimes neurological involvement. Among the treatments, enzyme replacement with imiglucerase is used. Objective: To evaluate the results of the application of imiglucerase in patients with Gaucher disease. Methods: A longitudinal, descriptive study to evaluate the behavior of the clinical, hematological and ultrasonographic variables of eight Cuban patients with Gaucher disease after receiving enzyme replacement treatment was carried out. They were evaluated after one, five and ten to fifteen years of treatment. Results: At debut, all patients presented anemia, and the majority showed thrombocytopenia and hepatosplenomegaly at diagnosis of the disease. Patients with neurological manifestations and the L444P mutation in a homozygous state were classified as type 3 GD, the rest as type 1. In all patients, an increase in hemoglobin levels, an increase in the number of platelets and a reduction in hepatosplenomegaly was observed after one year of treatment. Patients with type 3 maintain neurological involvement. No adverse reactions to the medication were reported. Conclusions: Enzyme replacement therapy with imiglucerase (Cerezyme®) is a fundamental pillar in the treatment of patients with this disease, which positively influences quality of life, obtaining better results with its onset in pediatric age.
Assuntos
Humanos , Epidemiologia Descritiva , Estudos LongitudinaisRESUMO
We evaluated retrospectively, efficacy and safety of taliglucerase alfa for Gaucher disease in a Brazilian population. Thirteen patients were included for efficacy analysis only one of them naïve to enzyme replacement therapy. All the parameters evaluated remained stable throughout treatment (mean duration 3,5years). Only three patients (out of 35) had to discontinue treatment due to a serious adverse event. In conclusion, treatment with taliglucerase alfa was found to be safe and efficient.
Assuntos
Terapia de Reposição de Enzimas/métodos , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Adulto , Idoso , Brasil/epidemiologia , Feminino , Doença de Gaucher/epidemiologia , Glucosilceramidase/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
La enfermedad de Gaucher es una entidad hereditaria del metabolismo de los esfingolípidos con un patrón de herencia autosómico recesivo determinada por una deficiencia de la actividad de la enzima b-glucosidasa ácida. En este trabajo se presentan 2 pacientes en edad pediátrica, uno del sexo femenino y otro del masculino, ambos con anemia y hepatoesplenomegalia confirmadas por ultrasonido. El aspirado de médula ósea mostró infiltración por células de almacenamiento, niveles bajos de la actividad enzimática de b-glucocerebrosidasa y el diagnóstico molecular de las posibles mutaciones conocidas confirmaron la enfermedad en ambos pacientes que se encuentran en tratamiento con terapia enzimática sustitutiva (imiglucerasa), con evolución favorable en los aspectos clínicos y humorales.
Gaucher's disease is a hereditary entity related to sphingolipids metabolism with an autosomal recessive hereditary pattern determined by a failure of the acid b-glucosidase enzyme. In present paper authors present the case of two pediatric patients (1 female and 1 male) both presenting with anemia and hepatosplenomegaly by ultrasound (US). Bone marrow aspirate showed infiltration by storage cells, low levels of enzymatic activity of b-glucocerebroside and a molecular diagnosis of potential known mutations confirmed the disease in both patients, who are under treatment with substitutive enzymatic therapy (imiglucerase) with a favorable course in clinical and humoral features.
Assuntos
Humanos , Masculino , Pré-Escolar , Criança , Feminino , Doença de Gaucher/terapia , Enzimas/uso terapêutico , beta-Glucosidase/deficiênciaRESUMO
Objetivo: Evaluar la respuesta terapéutica alcanzada con la administración del reemplazo enzimático con imiglucerasa en pacientes con enfermedad de Gaucher no neuronopática en la edad pediátrica. Pacientes y Métodos: Se realizo un estudio descriptivo prospectivo desde Enero 2007 hasta Marzo de 2008, se incluyeron 5 pacientes en edad pediátrica comprendida entre 3 y 14 años con diagnostico de Enfermedad de Gaucher no neuronopática que consultaron al hospital Dr. Adolfo Pons. Los 5 pacientes recibieron en forma continúa Imiglucerasa a dosis de 60 U/kg/peso cada 15 días, 3 pacientes durante un año y 2 pacientes durante 6 meses. Se evaluó el valor de la hemoglobina, cuenta blanca, plaquetas y disminución clínica de la visceromegalias, las cuales se determinaron antes y después del inicio de la Imiglucerasa cada 3 meses hasta 6 y 12 meses. Resultados: EL promedio de hemoglobina pretratamiento de los pacientes fue 9,72 ± 1,42 mientras que el nivel promedio al final de la observación fue de 11,84 ± 0,39 Cuenta blanca pretratamiento 4150 ± 2075,13 post tratamiento 7100 2488,97 Plaquetas Pretratamiento: 90280 ± 18135,37 al final 330800 ± 298706,72. Esplenomegalia pretratamiento El 75 % de los pacientes presentaron esplenomegalia leve a moderada al final de la observación 75% no tenia visceromegalia y el 25% presento disminución del 30% .Hepatomegalia: pretratamiento el 80% presento hepatomegalia leve a moderada al final de la observación 40 % resolvieron la hepatomegalia. Conclusiones: El reemplazo enzimático con imiglucerasa resulta eficaz para el tratamiento de la enfermedad de Gaucher no neoronopatica demostrado por la mejoría de los parámetros clínicos y de laboratorio .Siendo actualmente la alternativa terapéutica principal en la enfermedad con Gaucher.
To evaluate the therapeutic response reached with the administration of the enzymatic replacement with Imiglucerase in patients with non - neuropathic Gaucher disease in the pediatric age of the Dr. Adolfo Pons Hospital. Patients and Methods: This is a prospective descriptive study from January 2007 until March 2008, 5 patients were included in pediatric age understood between 3 and 14 years of both sexes (3 masculine sex and 2 feminine sex) by diagnosis of non - neuropathic Gaucher disease at the Dr Adolfo Pons Hospital, who were treated by enzymatic replacement with imiglucerase. The 5 received in continuous form Imiglucerase to dose of 60 U/kg/weight every 15 days,3 patients for one year and 2 patients for 6 months, appraisement the value of the hemoglobin, white count, and clinical decrease of the visceromegaly which were verify before and after the beginning of the imiglucerase every 3 months up to 6 and 12 months. Results: The average of hemoglobin pre-treatment of the patients was 9, 72 ± 1,42 whereas the average level at the end of the observation was of 11,84 ± 0,39. White count pre- treatment 4150± 2075, 13 post- treatment 7100 ±2488, 97. Platelets pre- Treatment: 90280 ±18135, 37 ultimately 330800 ± 298706, 72. Splenomegaly: pretreatment 75 % of the patients presented mild to moderate splenomegaly at the end of the observation, 75 % didnÊt have visceromegaly and 25 % presented decrease of 30 %. Hepatomegaly: pre- treatment the 80 % present hepatomegaly mild to moderate at the end of the observation 40 % solved the hepatomegaly. Conclusions: The enzymatic replacement with imiglucerase turns out to be effective for the treatment of the non - neuropathic Gaucher disease demonstrated by the improvement of the clinical parameters and of laboratory. Being nowadays the first therapeutic alternative for Gaucher disease treatment.
RESUMO
A doença de Gaucher tipo 1 é a doença de depósito lisossômico mais freqüente. De herança autossômica recessiva, é caracterizada pela deficiência da atividade da enzima glicocerebrosidase e o acúmulo patológico de seu substrato, a glicosilceramida, nas células da linhagem dos monócitos/macrófagos principalmente no baço, fígado e medula óssea. As manifestações são heterogêneas e incluem hepatoesplenomegalia, anemia, trombocitopenia, infiltração da medula óssea e lesões esqueléticas. Avaliaram-se os efeitos da terapia de reposição enzimática (TRE) sobre a anemia, trombocitopenia, hepatoesplenomegalia, estatura (crianças e adolescentes) e dor óssea em noventa pacientes com doença de Gaucher tipo 1 tratados por período de 24 meses no estado de São Paulo. Os principais sinais e sintomas antes do início do tratamento foram anemia (50 por cento), trombocitopenia (59 por cento), hepatomegalia (97 por cento), esplenomegalia (96 por cento), baixa estatura (46 por cento) e dor óssea (62 por cento). A dose média de TRE foi 35U/kg a cada duas semanas. A recuperação da anemia, da trombocitopenia e da dor óssea foi mais intensa aos seis meses de tratamento, e da hepatoesplenomegalia e da baixa estatura aos 18 meses. Após a melhora, a maioria dos pacientes manteve-se estável. Ao final de 24 meses de TRE, pelo menos 88 por cento dos pacientes atingiram os objetivos terapêuticos para anemia, 80 por cento para trombocitopenia, 34 por cento para hepatoesplenomegalia, 77 por cento para baixa estatura e 76 por cento para dor óssea. Novos estudos são necessários para avaliar a resposta terapêutica em longo prazo, principalmente em relação às alterações ósseas e de estatura, que podem apresentar resposta mais tardia e lenta.
Type 1 Gaucher's disease, the most common lysosomal storage disorder, is caused by an autosomal recessive deficiency of glucocerebrosidase that results in a pathologic accumulation of its substrate, glucocerebroside, in the cells of the monocyte/macrophage lineage mainly of the spleen, liver and bone marrow. The symptoms are heterogeneous and include hepatosplenomegaly, anemia, thrombocytopenia, bone marrow infiltration, and skeletal lesions. We evaluated the effects of enzyme replacement therapy (ERT) on anemia, thrombocytopenia, hepatosplenomegaly, growth retardation (children and adolescents) and bone pain among 90 patients with type 1 Gaucher's disease treated during 24 months in Sao Paulo State. Baseline signs and symptoms were anemia (50 percent), thrombocytopenia (59 percent), hepatomegaly (97 percent), splenomegaly (96 percent), growth retardation (46 percent) and bone pain (62 percent). The mean dose of ERT was 35 U/kg every two weeks. Reduction in anemia, thrombocytopenia and bone pain was greatest during the first six months of ERT and of hepatosplenomegaly and growth retardation within 18 months. Improvements were sustained by most of the patients during the follow-up. Within 24 months of ERT, therapeutic goals were achieved in at least 88 percent of patients with anemia, 80 percent with thrombocytopenia, 34 percent with hepatosplenomegaly, 77 percent with growth retardation and 76 percent with bone pain. Other studies are needed to evaluate the treatment efficacy over a longer period, mainly for skeletal lesions and growth retardation, which may present a slower recovery due to low penetration of imiglucerase in bones.