SABIIA - Sistema Aberto e Integrado de Informação em Agricultura (Sabiia)

Leistner,Sandra; Giugliani,Roberto.

Mucopolysaccharidoses (MPS) constitute, owing to their biochemical, genetical and clinical characteristics, a large and heterogeneous subgroup among the lysosomal storage diseases (LSD). They are caused by deficiency of specific enzymes, which are responsible for glycosaminoglycan (GAG) breakdown during different steps of its degradation pathway. MPS are responsible for about 32% of inborn errors of metabolism (IEM) and 54% of LSD identified in our laboratory (Regional Laboratory of Inborn Errors of Metabolism (RLIEM), Medical Genetics Unit, Hospital de Clínicas in Porto Alegre), which is a reference center for LSD diagnosis in Brazil. Therefore, we decided to set up a specific laboratory routine for detection and differential diagnosis of MPS in patients...

Ano: 1998

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47571998000100028

Palmero,Edenir Inêz; Campacci,Natalia; Schüler-Faccini,Lavinia; Giugliani,Roberto; Rocha,José Claudio Casali da; Vargas,Fernando Regla; Ashton-Prolla,Patricia.

Abstract In Brazil, the population in general has little knowledge about genetic risks, as well as regarding the role and importance of the Cancer Genetic Counseling (CGC). The goal of this study was to evaluate cancer-related worry and cancer risk perception during CGC sessions in Brazilian women at-risk for hereditary breast cancer. This study was performed in 264 individuals seeking CGC for hereditary breast cancer. Both cancer-affected and unaffected individuals were included. As results, individuals with and without cancer reported different motivations for seeking CGC and undergoing genetic testing. A correlation was observed between age at the first CGC session and age at which the closest relative was diagnosed with cancer. Multivariate analysis...

Clinical and biochemical findings in 7 patients with X-linked adrenoleukodystrophy treated with Lorenzo's Oil

Palavras-chave: Hereditary breast cancer; Hereditary cancer; Cancer-related worry; Cancer risk perception; Genetic counselling.

Ano: 2020

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000400104

Vargas,Carmen R.; Barschak,Alethéa G.; Coelho,Daniella M.; Furlanetto,Vivian; Souza,Carolina F.M. de; Karam,Simone M.; Jardim,Laura; Wajner,Moacir; Giugliani,Roberto.

X-Linked adrenoleukodystrophy (X-ALD) is a hereditary disorder of the peroxisomal metabolism biochemically characterized by the accumulation of very long chain fatty acids (VLCFA) in tissues and biological fluids. The major accumulated acids are hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0). The disorder is characterized clinically by central and peripheral demyelination and adrenal insufficiency closely related to the accumulation of fatty acids. The incidence of X-ALD is estimated to be 1:25,000 males. At least six phenotypes can be distinguished. The most common phenotypes are childhood cerebral ALD and adrenomyeloneuropathy (AMN). The recommended therapy consists of the use of the glyceroltrioleate/glyceroltrierucate (GTO/GTE) mixture, known...

Clinical research challenges in rare genetic diseases in Brazil

Ano: 2000

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572000000400001

Giugliani,Luciana; Vanzella,Claudia; Zambrano,Marina Bauer; Donis,Karina Carvalho; Wallau,Thaís Klassmann Wendland; Costa,Fernando Machado da; Giugliani,Roberto.

Abstract Rare diseases are defined as conditions with a prevalence of no more than 6.5 per 10,000 people. Although each rare disease individually affects a small number of people, collectively, the 6,000 to 8,000 rare conditions (80% of them with genetic cause) affect around 8% of the world’s population. Research about the natural history and underlying pathophysiological mechanisms of rare diseases, as well as clinical trials with new drugs, are important and necessary to develop new strategies for the treatment of these conditions. This report describes the experience of a clinical research group working with rare diseases in a reference center for lysosomal diseases in Brazil (Medical Genetics Service, Hospital de Clínicas de Porto Alegre). The...

Cockayne syndrome: report of a Brazilian family with confirmation of impaired RNA synthesis after UV-irradiation

Palavras-chave: Clinical research; Clinical investigation; Rare diseases; Lysosomal storage diseases; Enzyme replacement therapy.

Ano: 2019

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019000200305

Karam,Simone M.; Costa,Jaderson C.; Jardim,Laura; Pires,Ricardo F.; Lehmann,Alan R.; Giugliani,Roberto.

Cockayne syndrome (CS) is an autosomal recessive disorder characterized by dwarfism, growth deficiency, neurological deterioration, skin photosensitivity and a characteristic progressive facial appearance. In the present study we report the first Brazilian CS family in which diagnosis was confirmed by the demonstration of decreased RNA synthesis in cultured fibroblasts exposed to UV-C radiation. Despite the progressive course of the disease and the unavailability of an effective treatment, diagnosis may be very important for the benefits to be gained by the afflicted family from genetic counseling and/or prenatal diagnosis.

Common N-acetylgalactosamine-6-sulfate sulfatase (GALNS) exon mutations in Brazilian patients with mucopolysaccharidosis IVA (MPS IVA)

Ano: 2000

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572000000200005

Dieter,Tatiana; Matte,Ursula da Silveira; Schwartz,Ida Vanessa; Tomatsu,Shunji; Giugliani,Roberto.

Morquio A Syndrome (mucopolysaccharidosis IVA - MPS IVA, OMIM# 253000) is an autosomal recessive inborn error of metabolism caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). We investigated five unrelated Brazilian MPS IVA families for mutations in exons 4, 5, 9 and 10 of the GALNS gene. Six out of the 10 mutant alleles were identified. Taken together with a previous study, which included six unrelated families, common mutations among Brazilian patients were p.N164T, p.G116S and p.G301C. Among one hundred control subjects three novel silent mutations were found (p.A107A; GCC -> GCT, p.Y108Y; TAC -> TAT, p.P357P; CCG -> CCA). Screening starting with exons 4, 5, 9, 10 and 11 may be a good strategy for genotyping of...

Early infantile form of galactosialidosis in a female baby with a prenatal diagnosis of fetal ascites: First case in Brazil

Palavras-chave: GALNS mutations; GALNS mutation detection; Mucopolysaccharidosis IVA.

Ano: 2007

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572007000400004

Santos,Cláudia Maria Carvalho dos; Correia,Patrícia Santana; Rosa,Antônio Abílio Santa; Vaniazzi,Elde; Coelho,Janice Carneiro; Burin,Maira Graeff; Giugliani,Roberto; Fensom,Anthony H.; Oliveira,Cesário Paulo Honório de; Oliveira,Maria Lúcia Costa de; Llerena Jr.,Juan Clinton.

We present the first case of an early infantile form of galactosialidosis among Brazilians. This very rare and severe lysosomal storage disease has only a dozen patients clearly diagnosed worldwide. Clinical, pathological and biochemical features were consistent with previously published findings. We detected the disorder in a 7-month-old female baby with prenatal diagnosis of ascites. Evolution of the storage disease was monitored through routine thin-layer chromatography (TLC) for urinary oligosaccharides as part of a screening program for inborn errors of metabolism (IEM) in high-risk children, carried out in Rio de Janeiro.

Effects of gene therapy on cardiovascular symptoms of lysosomal storage diseases

Ano: 1998

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47571998000400005

Poletto,Edina; Pasqualim,Gabriela; Giugliani,Roberto; Matte,Ursula; Baldo,Guilherme.

Abstract Lysosomal storage diseases (LSDs) are inherited conditions caused by impaired lysosomal function and consequent substrate storage, leading to a range of clinical manifestations, including cardiovascular disease. This may lead to significant symptoms and even cardiac failure, which is an important cause of death among patients. Currently available treatments do not completely correct cardiac involvement in the LSDs. Gene therapy has been tested as a therapeutic alternative with promising results for the heart disease. In this review, we present the results of different approaches of gene therapy for LSDs, mainly in animal models, and its effects in the heart, focusing on protocols with cardiac functional analysis.

Evaluating enzyme replacement therapies for Anderson-Fabry disease: commentary on a recent report

Palavras-chave: Lysosomal storage disease; Gene therapy; Cardiovascular disease; Animal models; Heart.

Ano: 2019

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019000200261

Giugliani,Roberto; Westwood,Stephanie; Wellhoefer,Hartmann; Schenk,Jörn; Gurevich,Andrey; Kampmann,Christoph.

Abstract Anderson-Fabry disease (AFD) is a rare lysosomal storage disorder. Randomized controlled clinical trials (RCTs) are preferred as the highest category of evidence, but limited availability of robust evidence in rare diseases may necessitate the use of less rigorous evidence. An analysis of cohort studies of enzyme replacement therapies for AFD published in 2017 by El Dib and coworkers made treatment recommendations that contradict previously published findings from RCTs and a systematic Cochrane review. Our commentary outlines concerns regarding selection criteria and statistical methods with their analysis.

Fibroblasts of skin fragments as a tool for the investigation of genetic diseases: technical recommendations

Palavras-chave: Agalsidase alfa; Agalsidase beta; Anderson-Fabry disease; Enzyme replacement therapy.

Ano: 2018

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572018000500790

Coelho,Janice Carneiro; Giugliani,Roberto.

Skin biopsies are frequently indicated for investigation and/or confirmation of genetic disorders. Although relatively simple and noninvasive, these procedures require care in order to increase probability of success and to avoid patient discomfort and unnecessary repeated analyses and associated laboratory fees. The present report highlights the importance of skin biopsies in genetic disorder diagnosis and presents general rules for collecting, storing, transporting and processing samples. We recommend its reading to professionals intending to use this important and sometimes fundamental diagnostic tool.

Genomic rearrangements in BRCA1 and BRCA2: a literature review

Ano: 2000

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572000000200004

Ewald,Ingrid Petroni; Ribeiro,Patricia Lisboa Izetti; Palmero,Edenir Inêz; Cossio,Silvia Liliana; Giugliani,Roberto; Ashton-Prolla,Patricia.

Women with mutations in the breast cancer genes BRCA1 or BRCA2 have an increased lifetime risk of developing breast, ovarian and other BRCA-associated cancers. However, the number of detected germline mutations in families with hereditary breast and ovarian cancer (HBOC) syndrome is lower than expected based upon genetic linkage data. Undetected deleterious mutations in the BRCA genes in some high-risk families are due to the presence of intragenic rearrangements such as deletions, duplications or insertions that span whole exons. This article reviews the molecular aspects of BRCA1 and BRCA2 rearrangements and their frequency among different populations. An overview of the techniques used to screen for large rearrangements in BRCA1 and BRCA2 is also...

Guidelines for diagnosis and treatment of Hunter Syndrome for clinicians in Latin America

Palavras-chave: BRCA1; BRCA2; Breast cancer; Genomic rearrangements; MLPA.

Ano: 2009

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572009000300003

Giugliani,Roberto; Villarreal,Martha Luz Solano; Valdez,C. Araceli Arellano; Hawilou,Antonieta Mahfoud; Guelbert,Norberto; Garzón,Luz Norela Correa; Martins,Ana Maria; Acosta,Angelina; Cabello,Juan Francisco; Lemes,Aída; Santos,Mara Lucia Schmitz Ferreira; Amartino,Hernán.

This review aims to provide clinicians in Latin America with the most current information on the clinical aspects, diagnosis, and management of Hunter syndrome, a serious and progressive disease for which specific treatment is available. Hunter syndrome is a genetic disorder where iduronate-2-sulfatase (I2S), an enzyme that degrades glycosaminoglycans, is absent or deficient. Clinical manifestations vary widely in severity and involve multiple organs and tissues. An attenuated and a severe phenotype are recognized depending on the degree of cognitive impairment. Early diagnosis is vital for disease management. Clinical signs common to children with Hunter syndrome include inguinal hernia, frequent ear and respiratory infections, facial dysmorphisms,...

Information and Diagnosis Networks – tools to improve diagnosis and treatment for patients with rare genetic diseases

Palavras-chave: Hunter syndrome; Lysosomal disease; Iduronate-2-sulfatase; Enzyme replacement therapy; Treatment guidelines.

Ano: 2014

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572014000300003

Vieira,Taiane Alves; Trapp,Franciele Barbosa; Souza,Carolina Fischinger Moura de; Faccini,Lavínia Schuler; Jardim,Laura Bannach; Schwartz,Ida Vanessa Doederlein; Riegel,Mariluce; Vargas,Carmen Regla; Burin,Maira Graeff; Leistner-Segal,Sandra; Ashton-Prolla,Patrícia; Giugliani,Roberto.

Abstract Brazil is a country of continental dimensions and most genetic services are concentrated in the Southeast and South, including the Medical Genetics Service of the Hospital de Clínicas de Porto Alegre (MGS/HCPA). As many areas on the country do not have adequate medical genetics support, networks were designed to extend the service of the MGS/HCPA reference center. This paper presents the information and diagnosis networks that have their headquarters at MGS/HCPA: SIAT (National Information System on Teratogenic Agents), SIEM (Information Service on Inborn Errors of Metabolism), Alô Genética (Hello Genetics - Medical Genetics Information Service for Primary Health Care Professionals); Rede MPS Brasil (MPS-Mucopolysaccharidosis Brazil Network); Rede...

Lysosomal diseases: Overview on current diagnosis and treatment

Palavras-chave: Information services; Medical Genetics; Diagnostic networks; Rare diseases; Reference centers.

Ano: 2019

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019000200155

Poswar,Fabiano de Oliveira; Vairo,Filippo; Burin,Maira; Michelin-Tirelli,Kristiane; Brusius-Facchin,Ana Carolina; Kubaski,Francyne; Souza,Carolina Fischinger Moura de; Baldo,Guilherme; Giugliani,Roberto.

Abstract Lysosomal diseases (LDs), also known as lysosomal storage diseases (LSDs), are a heterogeneous group of conditions caused by defects in lysosomal function. LDs may result from deficiency of lysosomal hydrolases, membrane-associated transporters or other non-enzymatic proteins. Interest in the LD field is growing each year, as more conditions are, or will soon be treatable. In this article, we review the diagnosis of LDs, from clinical suspicion and screening tests to the identification of enzyme or protein deficiencies and molecular genetic diagnosis. We also cover the treatment approaches that are currently available or in development, including hematopoietic stem cell transplantation, enzyme replacement therapy, small molecules, and gene therapy.

Medical Genetics – Special issue dedicated to the 35th anniversary of the Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Brazil

Palavras-chave: Lysosomal storage diseases; Neonatal screening; Hematopoietic stem cell transplantation; Enzyme replacement therapy; Gene therapy.

Ano: 2019

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019000200165

Giugliani,Roberto.

Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in patients from the southern Brazilian city of Porto Alegre, RS

Ano: 2019

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019000200153

Castro,Simone M. de; Weber,Raquel; Matte,Úrsula; Giugliani,Roberto.

Glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) deficiency is one of the most common human enzymopathies throughout the world. Although most affected individuals are asymptomatic, there is a risk of neonatal jaundice and acute hemolytic anemia which can be triggered by infection, some pharmaceuticals and, in older individuals, eating fava beans. We characterized the molecular basis of G6PDH deficiency in a sample of 348 adults from Porto Alegre (population about 1.5 million), the capital of the southernmost Brazilian state of Rio Grande do Sul. Genomic DNA was extracted from peripheral blood leukocytes. We studied the three G6PDH mutations that appear to be the most frequent in Southern Brazil, the G202A and A376G A minus (A-) variants and the C563T...

Mucopolysacccharidoses: from understanding to treatment, a century of discoveries

Palavras-chave: G6PDH deficiency; Hemolytic anemia; Pentose pathway.

Ano: 2007

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572007000100003

Giugliani,Roberto.

After the first description of a patient recognized as a MPS case was made in 1917, several similar cases were described and identified. Observations reported in the middle of the twentieth century concerning the presence of acid mucopolysaccharides (later called glycosaminoglycans, or GAGs) in tissues and especially in urine of patients were instrumental in providing an identity for these diseases, which became referred as "mucopolysaccharidoses" (MPS). In the late 1960's it was demonstrated that MPS were caused by defects in the breakdown of GAGs, and the specific enzyme deficiencies for the 11 types and subtypes of MPS were identified thereafter. Genes involved in the MPS were subsequently identified, and a large number of disease-causing mutations were...

Mucopolysaccharidoses in northern Brazil: Targeted mutation screening and urinary glycosaminoglycan excretion in patients undergoing enzyme replacement therapy

Palavras-chave: Mucopoloysaccharidoses; Lysosomal diseases; Enzyme replacement therapy; Prenatal diagnosis; Newborn screening.

Ano: 2012

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572012000600006

Viana,Gustavo M.; Lima,Nathália O. de; Cavaleiro,Rosely; Alves,Erik; Souza,Isabel C.N.; Feio,Raimunda; Leistner-Segal,Sandra; Schwartz,Ida; Giugliani,Roberto; Silva,Luiz C. 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...

Mucopolysaccharidosis I, II, and VI: brief review and guidelines for treatment

Palavras-chave: Mucopolysaccharidosis; Enzyme replacement therapy; Mutations; Glycosaminoglycans.

Ano: 2011

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572011000300007

Giugliani,Roberto; Federhen,Andressa; Muñoz Rojas,Maria Verônica; Vieira,Taiane; Artigalás,Osvaldo; Lapagesse Pinto,Louise; Azevedo,Ana Cecília; Acosta,Angelina; Bonfim,Carmen; Lourenço,Charles Marques; Chong Ae,Kim; Horovitz,Dafne; Bonfim,Denize; Norato,Denise; Marinho,Diane; Palhares,Durval; Santos,Emerson Santana; Ribeiro,Erlane; Valadares,Eugênia; Guarany,Fábio; Lucca,Gisele Rosone de; Pimentel,Helena; Souza,Isabel Neves de; Correa Neto,Jordão; Fraga,José Carlos; Goes,José Eduardo; Cabral,José Maria; Simionato,José; Llerena Jr.,Juan; Jardim,Laura; Giuliani,Liane; Silva,Luiz Carlos Santana da; Santos,Mara L.; Moreira,Maria Angela; Kerstenetzky,Marcelo; Ribeiro,Márcia; Ruas,Nicole; Barrios,Patricia; Aranda,Paulo; Honjo,Rachel; Boy,Raquel; Costa,Ronaldo; Souza,Carolina; Alcantara,Flavio F.; Avilla,Silvio Gilberto A.; Fagondes,Simone; 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...

Neonatal screening for four lysosomal storage diseases with a digital microfluidics platform: Initial results in Brazil

Palavras-chave: Mucopolisaccharidoses; Hurler syndrome; Hunter syndrome; Maroteaux-Lamy syndrome; Enzyme replacement therapy; Treatment guidelines.

Ano: 2010

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000400001

Camargo Neto,Eurico; Schulte,Jaqueline; Pereira,Jamile; Bravo,Heydy; Sampaio-Filho,Claudio; Giugliani,Roberto.

Abstract We describe the initial results of a neonatal screening program for four lysosomal storage diseases (MPS I, Pompe, Gaucher and Fabry) using the digital microfluidics methodology. The method successfully identified patients previously diagnosed with these diseases and was used to test dried blood spot samples obtained from 10,527 newborns aged 2 to 14 days. The digital microfluidic technology shows potential for a simple, rapid and high-throughput screening for these four diseases in a standard neonatal screening laboratory.