Patients with mucopolysaccharidosis type VI (MPS VI) present with a wide range of disease severity and clinical manifestations, with significant functional impairment and shortened lifespan. Enzyme replacement therapy (ERT) with galsulfase has been shown to improve clinical and biochemical parameters including patient survival, quality of life and growth. The present study is a resurvey of 34 Brazilian MPS VI patients with rapidly progressive disease (classical phenotype) who initiated ERT with galsulfase under five years of age and had been on ERT until data collection in 2019, with few exceptions (n = 4 patients who died before 2019). Anthropometric measures, urinary glycosaminoglycans, and data regarding cardiac, orthopedic, neurologic, sleep apnea, hearing and ophthalmologic outcomes were filled in by specialists. Pubertal development, clinical complications, hospitalizations, and surgeries were also assessed. In this resurvey study, treatment with galsulfase has shown to be safe and well tolerated in MPS VI patients who initiated ERT under the age of 5 years and who have been undergoing ERT for approximately 10 years. Mortality rate suggests that early initiation of ERT may have a positive impact on patients' survival, improving but not preventing disease progression and death. MPS VI patients on ERT also showed improved growth velocity and the pubertal development was normal in all surviving patients. Follow-up data on pneumonia and hospitalization suggest that early ERT may have a protective effect against major respiratory complications. Cardiac valve disease progressed since their prior evaluation and spinal cord compression was observed in a large number of patients, suggesting that these disease complications were not modified by ERT.
Cognition/drug effects , Enzyme Replacement Therapy , Mucopolysaccharidosis VI/therapy , N-Acetylgalactosamine-4-Sulfatase/genetics , Adolescent , Brazil/epidemiology , Child , Child, Preschool , Female , Glycosaminoglycans/urine , Humans , Male , Mucopolysaccharidosis VI/enzymology , Mucopolysaccharidosis VI/pathology , Mucopolysaccharidosis VI/urine , N-Acetylgalactosamine-4-Sulfatase/therapeutic use , Phenotype , Quality of Life , Recombinant Proteins/genetics , Recombinant Proteins/therapeutic use , Severity of Illness Index
Objetivo: avaliar a qualidade de vida de pacientes com mucopolissacaridoses. Método: estudo do tipo série de casos, descritivo, realizado no Centro de Tratamento de Erros Inatos do Metabolismo. Utilizou-se o questionário de qualidade de vida SF-36. A coleta foi realizada durante o período de setembro a novembro de2014, sendo analisada no software Microsoft Office Excel-2010. Resultados: na avaliação pelo SF-36,observou-se que as dimensões com menores valores foram as de aspectos físicos (28,8) e as estado geral de saúde (50,3) e as com maiores valores foram as de saúde mental (73,8) e as de aspectos sociais (65,4).Conclusão: o questionário SF-36 mostrou-se um instrumento interessante para a avaliação da qualidade devida dos pacientes, pois permitiu detectar comprometimentos importantes em suas funções básicas.
Male , Female , Humans , Child , Adolescent , Adult , Metabolism, Inborn Errors , Mucopolysaccharidoses , Quality of Life , Enzyme Replacement Therapy , Epidemiology, Descriptive , Surveys and Questionnaires , Mucopolysaccharidoses/diagnosis
Gaucher Disease (GD) is a rare autosomal recessive disorder caused by the deficient activity of beta-glucocerebrosidase. GD is one of the lysosomal storage diseases with the most remarkable alterations in the immune system, and that may manifest clinically as autoimmune disorders and malignancy. We reported the immunological evaluation of a patient with GD and lupus nephritis. Decreased absolute values of T, and NK, and an inversion of CD4(+)/CD8(+) ratio, low levels of IgM and normal B cells were found when compared to reference values in a Brazilian population. Absence ofCD4(+)CD25(high)Foxp3(+) Treg and high levels of total NKT, iNKT cells and CD8(+) iNKT subsets were also observed when compared to the healthy control and GD patient without lupus nephritis. Treg subset and CD8(+) iNKT abnormalities might be involved in severe lupus nephritis in a GD patient. We conclude by emphasizing the importance of the immunological evaluation on early diagnosis of autoimmunity contributing to reduce mortality and morbidity of these patients.
B-Lymphocytes/immunology , Gaucher Disease/immunology , Glucosylceramidase/genetics , Killer Cells, Natural/immunology , Lupus Nephritis/immunology , Natural Killer T-Cells/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Brazil , Female , Forkhead Transcription Factors/metabolism , Gaucher Disease/genetics , Humans , Immunoglobulin M/blood , Interleukin-2 Receptor alpha Subunit/metabolism , Lupus Nephritis/genetics
OBJECTIVE: We studied the effect of long-term alglucerase/imiglucerase (Ceredase®/Cerezyme®, Genzyme, a Sanofi company, Cambridge, MA, USA) treatment on hematological, visceral, and bone manifestations of Gaucher disease type 1 (GD1). METHODS: The International Collaborative Gaucher Group (ICGG) Gaucher Registry identified GD1 patients treated with alglucerase/imiglucerase who had dose and clinical data at first infusion and after 10 years of follow-up. Data for hemoglobin, platelet count, organ volumes, bone pain, and bone crisis were analyzed. Tests of the null hypothesis (no change from first infusion to 10 years) were performed using t tests for within-patient absolute change in continuous measurements and McNemar/chi-square tests for change in distributions using categorical values. An alpha level of 0.05 designated statistical significance. RESULTS: As of October 2011, 557 nonsplenectomized and 200 splenectomized patients met the inclusion criteria. The majority of GD1 patients had at least one N370S allele. Compared with nonsplenectomized patients at first infusion, splenectomized patients had lower percentages of anemia (26.0 % vs. 42.8 %) and thrombocytopenia (14.2 % vs. 76.3 %), similar percentages of moderate or severe hepatomegaly (81.2 % vs. 80.0 %), and higher percentages of bone pain (88.9 % vs. 52.4 %) and bone crises (38.3 % vs. 16.0 %). After 10 years, both groups showed significant (p < 0.05) improvements in mean hemoglobin levels, platelet count, liver, and spleen (nonsplenectomized) volumes, and bone crises. Initial dosing in both groups ranged from <15 U/kg to ≤90 U/kg every 2 weeks. After 10 years, the majority was receiving 15 to ≤45 U/kg every 2 weeks. CONCLUSION: Ten years of imiglucerase treatment results in sustainable improvements in all GD1 parameters.
Gaucher Disease/drug therapy , Glucosylceramidase/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Enzyme Replacement Therapy , Female , Follow-Up Studies , Gaucher Disease/epidemiology , Humans , Male , Middle Aged , Registries/statistics & numerical data , Time Factors , Treatment Outcome , Young Adult
Gaucher disease -due to its low frequency- is considered an orphan disease. In 1991 the International Gaucher Registry was created and in 1992 the first patients from Latin America were enrolled. In 2008 the Latin American Group for Gaucher Disease was initiated. Its main objectives are to promote regional consensus, to stimulate the enrollment of patients into the International Gaucher Registry and the enhancement of knowledge on this disease, and to achieve better care and quality of life of patients in our Region. Until April 2010, 5828 patients have been enrolled all around the world, 911 (15.6%) from Latin America. This is the first comprehensive report of the disease in the Region. In our population there is a predominance of females, the most common clinical form is the type I (95%) and the age at diagnosis is before 20 years in 68% of patients. The most frequent clinical manifestations at diagnosis are splenomegaly (96%) and anemia (49%). Eighty percent of patients had radiographic findings of bone involvement. In our Region, the vast majority of patients (89%) had received enzyme replacement therapy with imiglucerase; with a long follow-up (up to 10 years) they have achieved the therapeutic goals, showing the great effectiveness of therapy. While the percentage of patients with therapy is high, discontinuations are common. The main deficiencies in our Region are: the lack of visceral volumetric evaluations and densitometries as well as molecular analysis for some patients. The main problem is the under-diagnosis of patients.
Gaucher Disease/diagnosis , Rare Diseases , Anemia/etiology , Enzyme Replacement Therapy , Female , Gaucher Disease/epidemiology , Gaucher Disease/therapy , Global Health/statistics & numerical data , Glucosylceramidase/therapeutic use , Humans , Latin America/epidemiology , Male , Rare Diseases/diagnosis , Rare Diseases/epidemiology , Rare Diseases/therapy , Sex Distribution , Splenomegaly/etiology
La enfermedad de Gaucher, por su escasa frecuencia, está incluida dentro de las llamadas enfermedades huérfanas. En 1991 se creó el Registro Internacional de Gaucher y en 1992 se incorporaron los primeros pacientes de Latinoamérica. En el año 2008 se creó el Grupo Latinoamericano para la Enfermedad de Gaucher (GLAEG) cuyos principales objetivos son fomentar la realización de consensos regionales, difundir el ingreso de pacientes al registro internacional y aumentar el conocimiento sobre la enfermedad para lograr mejorar la atención y la calidad de vida de los pacientes. Hasta abril del 2010 ingresaron 5828 pacientes de todo el mundo, 911 (15.6%) son de Latinoamérica. Este es el primer informe global de la enfermedad en la Región: hay un predominio del sexo femenino, la forma clínica más frecuente es el tipo I (95%); al diagnóstico la mayoría son <20 años (68%). Las manifestaciones clínicas más frecuentes al diagnóstico son esplenomegalia (96%) y anemia (49%), el 80% presentó hallazgos radiológicos de compromiso óseo. En nuestra Región, la gran mayoría de los pacientes (89%) ha recibido alguna vez terapia de reemplazo enzimática con imiglucerasa logrando, con un seguimiento prolongado (hasta10 años), las metas terapéuticas que muestran la gran eficacia de la terapia. Si bien el porcentaje de pacientes con terapia es alto, las suspensiones de tratamiento son frecuentes. Las principales deficiencias en nuestra Región son: la carencia de evaluaciones viscerales volumétricas, de densitometría y de estudios moleculares en algunos pacientes. El principal problema es el subdiagnóstico.
Gaucher disease -due to its low frequency- is considered an orphan disease. In 1991 the International Gaucher Registry was created and in 1992 the first patients from Latin America were enrolled. In 2008 the Latin American Group for Gaucher Disease was initiated. Its main objectives are to promote regional consensus, to stimulate the enrolment of patients into the International Gaucher Registry and the enhancement of knowledge on this disease, and to achieve better care and quality of life of patients in our Region. Until April 2010, 5828 patients have been enrolled all around the world, 911 (15.6%) from Latin America. This is the first comprehensive report of the disease in the Region. In our population there is a predominance of females, the most common clinical form is the type I (95%) and the age at diagnosis is before 20 years in 68% of patients. The most frequent clinical manifestations at diagnosis are splenomegaly (96%) and anemia (49%). Eighty percent of patients had radiographic findings of bone involvement. In our Region, the vast majority of patients (89%) had received enzyme replacement therapy with imiglucerase; with a long follow-up (up to 10 years) they have achieved the therapeutic goals, showing the great effectiveness of therapy. While the percentage of patients with therapy is high, discontinuations are common. The main deficiencies in our Region are: the lack of visceral volumetric evaluations and densitometries as well as molecular analysis for some patients. The main problem is the under-diagnosis of patients.
Female , Humans , Male , Gaucher Disease/diagnosis , Rare Diseases , Anemia/etiology , Enzyme Replacement Therapy , Gaucher Disease/epidemiology , Gaucher Disease/therapy , Glucosylceramidase/therapeutic use , Latin America/epidemiology , Rare Diseases/diagnosis , Rare Diseases/epidemiology , Rare Diseases/therapy , Sex Distribution , Splenomegaly/etiology , Global Health/statistics & numerical data
La enfermedad de Gaucher, por su escasa frecuencia, está incluida dentro de las llamadas enfermedades huérfanas. En 1991 se creó el Registro Internacional de Gaucher y en 1992 se incorporaron los primeros pacientes de Latinoamérica. En el año 2008 se creó el Grupo Latinoamericano para la Enfermedad de Gaucher (GLAEG) cuyos principales objetivos son fomentar la realización de consensos regionales, difundir el ingreso de pacientes al registro internacional y aumentar el conocimiento sobre la enfermedad para lograr mejorar la atención y la calidad de vida de los pacientes. Hasta abril del 2010 ingresaron 5828 pacientes de todo el mundo, 911 (15.6%) son de Latinoamérica. Este es el primer informe global de la enfermedad en la Región: hay un predominio del sexo femenino, la forma clínica más frecuente es el tipo I (95%); al diagnóstico la mayoría son <20 años (68%). Las manifestaciones clínicas más frecuentes al diagnóstico son esplenomegalia (96%) y anemia (49%), el 80% presentó hallazgos radiológicos de compromiso óseo. En nuestra Región, la gran mayoría de los pacientes (89%) ha recibido alguna vez terapia de reemplazo enzimática con imiglucerasa logrando, con un seguimiento prolongado (hasta10 años), las metas terapéuticas que muestran la gran eficacia de la terapia. Si bien el porcentaje de pacientes con terapia es alto, las suspensiones de tratamiento son frecuentes. Las principales deficiencias en nuestra Región son: la carencia de evaluaciones viscerales volumétricas, de densitometría y de estudios moleculares en algunos pacientes. El principal problema es el subdiagnóstico.(AU)
Gaucher disease -due to its low frequency- is considered an orphan disease. In 1991 the International Gaucher Registry was created and in 1992 the first patients from Latin America were enrolled. In 2008 the Latin American Group for Gaucher Disease was initiated. Its main objectives are to promote regional consensus, to stimulate the enrolment of patients into the International Gaucher Registry and the enhancement of knowledge on this disease, and to achieve better care and quality of life of patients in our Region. Until April 2010, 5828 patients have been enrolled all around the world, 911 (15.6%) from Latin America. This is the first comprehensive report of the disease in the Region. In our population there is a predominance of females, the most common clinical form is the type I (95%) and the age at diagnosis is before 20 years in 68% of patients. The most frequent clinical manifestations at diagnosis are splenomegaly (96%) and anemia (49%). Eighty percent of patients had radiographic findings of bone involvement. In our Region, the vast majority of patients (89%) had received enzyme replacement therapy with imiglucerase; with a long follow-up (up to 10 years) they have achieved the therapeutic goals, showing the great effectiveness of therapy. While the percentage of patients with therapy is high, discontinuations are common. The main deficiencies in our Region are: the lack of visceral volumetric evaluations and densitometries as well as molecular analysis for some patients. The main problem is the under-diagnosis of patients.(AU)
Female , Humans , Male , Gaucher Disease/diagnosis , Rare Diseases , Anemia/etiology , Enzyme Replacement Therapy , Gaucher Disease/epidemiology , Gaucher Disease/therapy , Glucosylceramidase/therapeutic use , Latin America/epidemiology , Rare Diseases/diagnosis , Rare Diseases/epidemiology , Rare Diseases/therapy , Sex Distribution , Splenomegaly/etiology , Global Health/statistics & numerical data
Mucopolysaccharidoses (MPS) are rare genetic diseases caused by deficiency of specific lysosomal enzymes that affect catabolism of glycosaminoglycans (GAG). Accumulation of GAG in various organs and tissues in MPS patients results in a series of signs and symptoms, producing a multisystemic condition affecting bones and joints, the respiratory and cardiovascular systems and many other organs and tissues, including in some cases, cognitive performance. So far, eleven enzyme defects that cause seven different types of MPS have been identified. Before introduction of therapies to restore deficient enzyme activity, treatment of MPS focused primarily on prevention and care of complications, still a very important aspect in the management of these patients. In the 80's treatment of MPS with bone marrow transplantation/hematopoietic stem cells transplantation (BMT/HSCT) was proposed and in the 90's, enzyme replacement therapy (ERT),began to be developed and was approved for clinical use in MPS I, II and VI in the first decade of the 21st century. The authors of this paper are convinced that a better future for patients affected by mucopolysaccharidoses depends upon identifying, understanding and appropriately managing the multisystemic manifestations of these diseases. This includes the provision of support measures (which should be part of regular multidisciplinary care of these patients) and of specific therapies. Although inhibition of synthesis of GAG and the recovery of enzyme activity with small molecules also may play a role in the management of MPS, the breakthrough is the currently available intravenous ERT. ERT radically changed the setting for treatment of mucopolysaccharidosis I, II and VI in the last decade., Benefits can even be extended soon to MPS IV A (ERT for this condition is already in clinical development), with prediction for treatment of MPS III A and the cognitive deficit in MPS II by administration of the enzyme directly into the central nervous system (CNS). A large number of Brazilian services, from all regions of the country, already have experience with ERT for MPS I, II and VI. This experience was gained not only by treating patients but also with the participation of some groups in clinical trials involving ERT for these conditions. Summing up the three types of MPS, more than 250 patients have already been treated with ERT in Brazil. The experience of professionals coupled to the data available in international literature, allowed us to elaborate this document, produced with the goal of bringing together and harmonize the information available for the treatment of these severe and progressive diseases, which, fortunately, are now treatable, a situation which bring new perspectives for Brazilian patients, affected by these conditions.
Enzyme Replacement Therapy/methods , Mucopolysaccharidoses/drug therapy , Brazil , Enzyme Replacement Therapy/statistics & numerical data , Humans , Mucopolysaccharidoses/classification , Practice Guidelines as Topic
Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.
Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.
Enzyme Replacement Therapy , Glycosaminoglycans , Mucopolysaccharidosis VI , Nutrition Policy
As mucopolissacaridoses (MPS) são doenças genéticas raras causadas pela deficiência de enzimas lisossômicas específicas que afetam o catabolismo de glicosaminoglicanos (GAG). O acúmulo de GAG em vários órgãos e tecidos nos pacientes afetados pelas MPS resulta em uma série de sinais e sintomas, integrantes de um quadro clínico multissistêmico que compromete ossos e articulações, vias respiratórias, sistema cardiovascular e muitos outros órgãos e tecidos, incluindo, em alguns casos, as funções cognitivas. Já foram identificados 11 defeitos enzimáticos que causam sete tipos diferentes de MPS. Antes do advento de terapias dirigidas para a restauração da atividade da enzima deficiente, o tratamento das MPS tinha como principal foco a prevenção e o cuidado das complicações, aspecto ainda bastante importante no manejo desses pacientes. Na década de 80 foi proposto o tratamento das MPS com transplante de medula óssea/transplante de células tronco hematopoiéticas (TMO/TCTH) e na década de 90 começou o desenvolvimento da Terapia de Reposição Enzimática (TRE), que se tornou uma realidade aprovada para uso clínico nas MPS I, II e VI na primeira década do século 21. Os autores deste trabalho têm a convicção de que um melhor futuro para os pacientes afetados pelas MPS depende da identificação, compreensão e manejo adequado das manifestações multissistêmicas dessas doenças, incluindo medidas de suporte (que devem fazer parte da assistência multidisciplinar regular destes pacientes) e terapias específicas...
Mucopolysaccharidoses (MPS) are rare genetic diseases caused by deficiency of specific lysosomal enzymes that affect catabolism of glycosaminoglycans (GAG). Accumulation of GAG in various organs and tissues in MPS patients results in a series of signs and symptoms, producing a multisystemic condition affecting bones and joints, the respiratory and cardiovascular systems and many other organs and tissues, including in some cases, cognitive performance. So far, eleven enzyme defects that cause seven different types of MPS have been identified. Before introduction of therapies to restore deficient enzyme activity, treatment of MPS focused primnarily on prevention and care of complications, still a very important aspect in the management of these patients. In the 80's treatment of MPS with bone marrow transplantation/hematopoietic stem cells transplantation (BMT/HSCT) was proposed and in the 90's, enzyme replacement therapy (ERT),began to be developed and was approved for clinical use in MPS I, II and VI in the first decade of the 21st century. The authors of this paper are convinced that a better future for patients affected by mucopolysaccharidoses depends upon identifying, understanding and appropriately managing the multisystemic manifestations of these diseases. This includes the provision of support measures (which should be part of regular multidisciplinary care of these patients) and of specific therapies...
Humans , Enzyme Replacement Therapy/methods , Mucopolysaccharidoses/drug therapy , Brazil , Enzyme Replacement Therapy , Mucopolysaccharidoses/classification , Practice Guidelines as Topic
A doença de Gaucher (DG) é um erro inato do metabolismo do grupo das doenças lisossômicas de depósito, sendo a mais freqüente do referido grupo. É de herança autossômica recessiva, portanto com risco de 25 por cento a cada gestação de casal heterozigoto. A doença é resultante da deficiência da beta-glicosidase ácida ou beta-glicocerebrosidase, que leva ao acúmulo de glicolipídios nos macrófagos principalmente em baço, fígado, medula óssea e pulmão. As manifestações clínicas ou fenotípicas da DG vão depender do grau de deficiência da enzima, existindo três tipos: Tipo I, forma não neuropática, afeta crianças e adultos com hepatoesplenomegalia, anemia, trombocitopenia, leucopenia e lesões ósseas; Tipo II, forma neuropática aguda, afeta crianças com 4-5 meses com quadro neurológico grave, hepatoesplenomegalia e comprometimento pulmonar e o Tipo III, forma neuropática crônica, afeta crianças e adolescentes com quadro neurológico menos grave que o Tipo II e ainda pode comprometer fígado, baço e ossos. Um grupo de catorze médicos com experiência no tratamento da DG com reposição enzimática realizaram extensa revisão da literatura, confrontaram com os dados evolutivos dos pacientes brasileiros e chegaram a um consenso quanto aos critérios para iniciar o tratamento, a dose da enzima e freqüência das infusões, do acompanhamento ambulatorial, laboratorial e radiológico. O Grupo Brasileiro de Estudos em Doença de Gaucher e outras Doenças de Depósito Lisossômico (GBDDL) tem o objetivo de estabelecer diretrizes para o diagnostico, tratamento e acompanhamento de pacientes com doença de Gaucher no Brasil. Esta iniciativa pioneira visa uniformizar a conduta no país com relação ao tratamento de DG com reposição enzimática, tratamento de alto custo porém de grande eficácia
Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Adult , Humans , Gaucher Disease/diagnosis , Gaucher Disease/therapy
