Navegando por Autor "SOUZA, Isabel Cristina Neves de"

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CYP21 gene mutations in Brazilian patients with 21-hydroxylase deficiency from the Amazon region
(2008) CARVALHO, Tarcísio André Amorim de; SOUZA, Isabel Cristina Neves de; YOSHIOKA, France Keiko Nascimento; CALDATO, Milena Coelho Fernandes; TORRES, Nilza Nei; GARCIA, Lena Stilianidi; GUERREIRO, João Farias
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (P450c21, CYP21) accounts for about 95% of all CAH cases. The incidence of CYP21 gene mutations has been extensively studied in the last years, but in Brazil it has been investigated only in Southeast Brazilian patients. This study is the first report on the distribution of CYP21 mutations in patients from the Amazon region. Direct sequencing of the CYP21 gene identified at least one mutation in 96% of the studied chromosomes. The most common mutations found were IVS2-13A/C > G (36%), Q318X (12%), V281L (12%), 1760_1761insT (9%), Cluster E6 (7%), and P30L (7%). The worldwide most common mutations were identified among patients from the Amazon region at frequencies that may be expected for a population resulting from the admixture of Europeans (predominantly Portuguese), African Blacks and Amerindians, in proportions that differ from those estimated for South Brazilian populations. Interethnic mixture may explain the differences in the frequencies of some mutations between Brazilian patients from the Amazon and from the Southeast of the country. However, the differences found may also be due to variation in the number of patients with the different clinical forms of 21-hydroxylase deficiency in the studies carried out so far.
Acesso aberto (Open Access)
Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network
(2014) DORNELLES, Alicia Dorneles; PINTO, Louise Lapagesse de Carmargo; PAULA, Ana Carolina de; STEINER, Carlos Eduardo; LOURENÇO, Charles Marques; KIM, Chong Ae; HOROVITZ, Dafne Dain Gandelman; RIBEIRO, Erlane Marques; VALADARES, Eugênia Ribeiro; GOULART, Isabela; SOUZA, Isabel Cristina Neves de; NERI, João Ivanildo da Costa Ferreira; SILVA, Luiz Carlos Santana da; SILVA, Luiz Roberto; RIBEIRO, Márcia Gonçalves; OLIVEIRA SOBRINHO, Ruy Pires de; GIUGLIANI, Roberto; SCHWARTZ, Ida Vanessa Doederlein
Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ≥ ± 20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.
Acesso aberto (Open Access)
Mucopolysaccharidoses in northern Brazil: targeted mutation screening and urinary glycosaminoglycan excretion in patients undergoing enzyme replacement therapy
(2011) VIANA, Gustavo Monteiro; LIMA, Nathalia Oliveira de; CAVALEIRO, Rosely Maria dos Santos; ALVES, Erik Artur Cortinhas; SOUZA, Isabel Cristina Neves de; FEIO, Raimunda Helena; LEISTNER-SEGAL, Sandra; SCHWARTZ, Ida Vanessa Doederlein; GIUGLIANI, Roberto; SILVA, Luiz Carlos Santana da
Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patients' clinical signs. We studied biochemical and molecular characteristics of nine MPS patients (two MPS I, four MPS II and three MPS VI) undergoing ERT in northern Brazil. The responsiveness of ERT was evaluated through urinary GAG excretion measurements. Patients were screened for eight common MPS mutations, using PCR, restriction enzyme tests and direct sequencing. Two MPS I patients had the previously reported mutation p.P533R. In the MPS II patients, mutation analysis identified the mutation p.R468W, and in the MPS VI patients, polymorphisms p.V358M and p.V376M were also found. After 48 weeks of ERT, biochemical analysis showed a significantly decreased total urinary GAG excretion in patients with MPS I (p < 0.01) and MPS VI (p < 0.01). Our findings demonstrate the effect of ERT on urinary GAG excretion and suggest the adoption of a screening strategy for genotyping MPS patients living far from the main reference centers.
Acesso aberto (Open Access)
Mucopolysaccharidosis I, II, and VI: brief review and guidelines for treatment
(2010) GIUGLIANI, Roberto; FEDERHEN, Andressa; MUÑOZ ROJAS, Maria Verónica; VIEIRA, Taiane Alves; ARTIGALÁS, Osvaldo Alfonso Pinto; PINTO, Louise Lapagesse de Carmargo; AZEVEDO, Ana Cecília Medeiros Mano; ACOSTA, Angelina Xavier; BONFIM, Carmem Maria Sales; LOURENÇO, Charles Marques; KIM, Chong Ae; HOROVITZ, Denize Bonfim; NORATO, Denise Yvonne Janovitz; MARINHO, Diane Ruschel; PALHARES, Durval Batista; SANTOS, Emerson Santana; RIBEIRO, Erlane Marques; VALADARES, Eugênia Ribeiro; GUARANY, Fábio Coelho; LUCCA, Gisele Rosone de; PIMENTEL, Helena; SOUZA, Isabel Cristina Neves de; CORRÊA NETO, Jordão; FRAGA, José Carlos; GÓES, José Eduardo Coutinho; CABRAL, José Maria; SIMIONATO, José; LLERENA JUNIOR, Juan Clinton; JARDIM, Laura Bannach; GIULIANI, Liane de Rosso; SILVA, Luiz Carlos Santana da; SANTOS, Mara Lucia Schmitz Ferreira; MOREIRA, Maria Ângela; KERSTENETZKY, Marcelo Soares; RIBEIRO, Márcia Gonçalves; GUARANY, Nicole Ruas; BARRIOS, Patricia Martins Moura; ARANDA, Paulo Cesar; HONJO, Rachel Sayuri; SILVA, Raquel Tavares Boy da; COSTA, Ronaldo; SOUZA, Carolina Fischinger Moura de; ALCANTARA, Flavio Ferraz de Paes e; AVILLA, Sylvio Gilberto Andrade; FAGONDES, Simone Chaves; MARTINS, Ana Maria
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.
Acesso aberto (Open Access)
Terapia de reposição enzimática para as mucopolissacaridoses I, II e VI: recomendações de um grupo de especialistas brasileiros
(2010) GIUGLIANI, Roberto; FEDERHEN, Andressa; MUÑOZ ROJAS, Maria Verónica; VIEIRA, Taiane Alves; ARTIGALÁS, Osvaldo Alfonso Pinto; PINTO, Louise Lapagesse de Carmargo; AZEVEDO, Ana Cecília Medeiros Mano; ACOSTA, Angelina Xavier; BOMFIM, Carmem; LOURENÇO, Charles Marques; KIM, Chong Ae; HOROVITZ, Dafne Dain Gandelman; SOUZA, Denize Bomfim; NORATO, Denise Yvonne Janovitz; MARINHO, Diane Ruschel; PALHARES, Durval Batista; SANTOS, Emerson Santana; RIBEIRO, Erlane Marques; VALADARES, Eugênia Ribeiro; GUARANY, Fábio Coelho; LUCCA, Gisele Rosone de; PIMENTEL, Helena; SOUZA, Isabel Cristina Neves de; CORRÊA NETO, Jordão; FRAGA, José Carlos; GÓES, José Eduardo Coutinho; CABRAL, José Maria; SIMIONATO, José; LLERENA JUNIOR, Juan Clinton; JARDIM, Laura Bannach; GIULIANI, Liane de Rosso; SILVA, Luiz Carlos Santana da; SANTOS, Mara Lucia Schmitz Ferreira; MOREIRA, Maria Ângela; KERSTENETZKY, Marcelo Soares; RIBEIRO, Márcia Gonçalves; GUARANY, Nicole Ruas; BARRIOS, Patricia Martins Moura; ARANDA, Paulo Cesar; HONJO, Rachel Sayuri; SILVA, Raquel Tavares Boy da; COSTA, Ronaldo; SOUZA, Carolina Fischinger Moura de; ALCANTARA, Flavio Ferraz de Paes e; AVILLA, Sylvio Gilberto Andrade; FAGONDES, Simone Chaves; MARTINS, Ana Maria
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. 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.