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Giugliani R.,Federal University of Rio Grande do Sul | Giugliani R.,Collaborating Center for the Development of Medical Genetic Services in Latin America | Giugliani R.,Instituto Nacional Of Genetica Medica Populacional Inagemp
Journal of Inherited Metabolic Disease | Year: 2012

The aim of newborn screening (NBS) programs is to detect a condition in a presymptomatic baby and provide management measures which could significantly improve the natural history of the disease. NBS programs for metabolic diseases were first introduced in North America and Europe and in the 1960s for phenylketonuria, expanded a few years later to include congenital hypothyroidism, and have been growing steadily in terms of number of conditions tested for and number of countries and births covered. Lysosomal storage diseases (LSDs) are a group of around 50 genetic conditions in which a defect in a lysosomal function occurs. LSDs are progressive conditions, being usually asymptomatic at birth, but with clinical features becoming apparent in childhood, with severe manifestations in most instances, high morbidity and shortened life span. Although individually rare, the prevalence of LSDs is significant when the group is considered as a whole (around 1:4,000-1:9,000 live births). Several management techniques, including bone marrow transplantation, enzyme replacement therapy, substrate inhibition therapy, pharmacological chaperones and many other approaches are transforming the LSDs into treatable conditions. However, lack of awareness and lack of access to tests cause a significant delay between onset of symptoms and diagnosis. Several lines of evidence showing that the earlier introduction of therapy may provide a better outcome, are bringing support to the idea of including LSDs in NBS programs. Due to advances in technology, high-throughput multiplex methods are now available for mass screening of several LSDs. Pilot projects were already developed in many countries for some LSDs, with interesting results. Although some NBS in Latin America has been carried out since the 1970s, it has so far been incorporated as a public health program in only a few countries in the region. It will probably take many years before NBS is implemented in most Latin American countries with a comprehensive coverage in terms of number of diseases and number of births. Population medical genetics is the area of medical genetics that aims at the study and medical care of the population, and not of the family, which is the case for clinical or medical genetics itself. It combines different aspects of genetics: clinical genetics; human population genetics, which investigates populations according to micro-evolutionary parameters; epidemiological genetics, traditionally involved in the study of common chronic diseases of polygenic etiology, except for Mendelian diseases; and sanitary or community genetics, which stands at the interface with public health, giving support to preventive health measures. Taking into account that several LSDs were identified in a higher frequency in selected areas and/or populations, the population medical genetics approach could help to introduce the NBS for LSDs in the region, with identification of areas with higher risk for selected diseases and design of customized screening program to address specific needs. As an example of the potential of this approach, a pilot program of NBS for MPS VI was implemented in a community from North East Brazil where 13 cases of MPS VI were identified in an area with 50,000 inhabitants. This program, which will enable not only identification and early treatment of affected newborns but also carrier detection, and which would allow genetic counseling for at-risk couples, could be an alternative model for a customized NBS of LSDs to be carried out in selected regions. © SSIEM and Springer 2011.

Pedroso J.L.,Federal University of Sao Paulo | de Souza P.V.S.,Federal University of Sao Paulo | Pinto W.B.V.D.R.,Federal University of Sao Paulo | Braga-Neto P.,State University of Ceara | And 6 more authors.
Parkinsonism and Related Disorders | Year: 2015

Introduction: The combination of cerebellar ataxia and spasticity is common. However, autosomal dominant genetic diseases presenting with spastic-ataxia are a smaller group. Pyramidal signs have been frequently observed in several SCA subtypes, particularly in spinocerebellar ataxia type 1. Methods: We prospectively evaluated the pyramidal signs and spasticity in SCA1 patients, and correlated the data with genetic and clinical features. Results: In this study, we observed that spasticity may be an early and presenting feature of SCA1, since 3 patients had pyramidal signs and spasticity as the first neurological sign. SCA1 patients with spasticity were significantly younger. Conclusion: SCA1 may rarely present with pure spastic paraplegia, resembling hereditary spastic paraplegia, before the appearance of cerebellar signs. This observation may confuse the neurologist when a genetic testing is requested for an autosomal dominant spastic paraplegia, directing research to hereditary spastic paraplegia group. © 2015 Elsevier Ltd.

Wehby G.L.,University of Iowa | Wehby G.L.,National Bureau of Economic Research | Gili J.A.,CONICET | Pawluk M.,CONICET | And 2 more authors.
International Journal of Public Health | Year: 2015

Objectives: We examine disparities in birth weight and gestational age by ethnic ancestry in 2000–2011 in eight South American countries. Methods: The sample included 60,480 singleton live births. Regression models were estimated to evaluate differences in birth outcomes by ethnic ancestry controlling for time trends. Results: Significant disparities were found in seven countries. In four countries—Brazil, Ecuador, Uruguay, and Venezuela—we found significant disparities in both low birth weight and preterm birth. Disparities in preterm birth alone were observed in Argentina, Bolivia, and Colombia. Several differences in continuous birth weight, gestational age, and fetal growth rate were also observed. There were no systematic patterns of disparities between the evaluated ethnic ancestry groups across the study countries, in that no racial/ethnic group consistently had the best or worst outcomes in all countries. Conclusions: Racial/ethnic disparities in infant health are common in several South American countries. Differences across countries suggest that racial/ethnic disparities are driven by social and economic mechanisms. Researchers and policymakers should acknowledge these disparities and develop research and policy programs to effectively target them. © 2014, Swiss School of Public Health.

Saute J.A.M.,Hospital de Clinicas de Porto Alegre HCPA | Jardim L.B.,Hospital de Clinicas de Porto Alegre HCPA | Jardim L.B.,Federal University of Rio Grande do Sul | Jardim L.B.,Instituto Nacional Of Genetica Medica Populacional Inagemp
Expert Opinion on Orphan Drugs | Year: 2015

Introduction: Spinocerebellar ataxia (SCA) type 3/Machado-Joseph disease (SCA3/MJD) is the most common SCA worldwide. SCA3/MJD is an adult onset cerebellar ataxia associated with pyramidal, lower motor neuron and extrapyramidal findings, resulting in heterogeneous phenotypic presentations. SCA3/MJD is caused by a CAG repeat expansion at the ATXN3 gene that codes for ataxin-3. Mutant ataxin-3 trigger multiple, interconnected pathogenic cascades, but many of key disease mechanisms remain unclear. Areas covered: This review focused on the present knowledge about the genetic characteristics, ancestral origins, selective forces, clinical course and determinants of phenotypic heterogeneity of SCA3/MJD. Disease-modifying and symptomatic therapies were also detailed. Expert opinion: Although no evidence exists for disease-modifying therapies for SCA3/MJD, symptomatic treatments for some disease signs are available. Genetic counseling is fundamental and should include discussion on options such as prenatal or pre-implantation diagnoses, and adoption, as ways to prevent the disease. Basic and translational science trying to speed the exchange of novel therapies (e.g., gene silencing) to the clinics will be central to the development of effective therapies, together with consortiums to define surrogate disease biomarkers and essential data for planning future clinical trials on SCA3/MJD. © 2015 Informa UK, Ltd.

Pitroski C.E.,Federal University of Rio Grande do Sul | Cossio S.L.,Instituto Nacional Of Genetica Medica Populacional Inagemp | Cossio S.L.,Federal University of Rio Grande do Sul | Koehler-Santos P.,Federal University of Rio Grande do Sul | And 4 more authors.
International Journal of Colorectal Disease | Year: 2011

Introduction MUTYH-associated polyposis (MAP) is an autosomal recessive cancer predisposition syndrome associated with the development of colorectal tumors and colonic polyps at an early age. MAP syndrome is associated to germline biallelic mutations in the MUTYH gene which lead to deficient DNA repair through the base-excision repair system and accumulation of G:C?T:A transversions. Occurrence of such mutations in oncogenes and tumor suppressor genes drives colorectal carcinogenesis and is associated with the development of colonic polyps. Two common mutations, p.Y179C and p.G396D, are present in approximately 70-80% of MAP in European families with identified MUTYH germline mutations. The aim of this study was to assess the frequency of the germline MUTYH mutations p.Y179C and p.G396D in Brazilian patients with MAP and other hereditary colorectal cancer (CRC) phenotypes, as well as in sporadic CRC cases. Materials and methods A total of 75 patients were included. Samples were screened for the MUTYH germline mutations p.Y179C and p.G396D by allelic discrimination assays using allele-specific TaqMan® probes. In all mutationpositive cases, results were confirmed by sequencing. Results and conclusions Biallelic germline MUTYH mutations were identified in 4 of 60 (6.6%) patients with a phenotype of hereditary colorectal cancer. Germline MUTYH mutation screening should be considered in the differential diagnosis of hereditary colorectal syndromes, and not only in MAP, but also in familial adenomatous polyposis and Bethesda criteria-positive families. Additional mutation screening studies of the MUTYH gene in a larger number of Brazilian patients will be necessary to confirm these results and determine the validity and applicability of MUTYH mutation screening in our population. © 2011 Springer-Verlag.

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