Patrícia Santana Correia

A clinical study of 77 patients with mucopolysaccharidosis type II

Aim: This study aims to assess the clinical features of 77 South American patients (73 Brazilian) with mucopolysaccharidosis type II (MPS II).

Analysis of the human Sonic Hedgehog coding and promoter regions in sacral agenesis, triphalangeal thumb, and mirror polydactyly

Abstract The human Sonic Hedgehog gene (SHH) is one of the vertebrate homologs related to the Drosophila segment polarity gene hedgehog. The entire coding and promoter region of the SHH gene, including 2 kb 5’ of the transcriptional start site has been screened for mutations in families with autosomal dominant sacral agenesis and autosomal dominant triphalangeal thumb, two conditions previously known to be linked to 7q36. We have also studied the SHH gene in five families with mirror polydactyly associated with tibial hemimelia and in 51 unrelated patients with neural tube defects. Except for two sequence variants in exon 3, no mutations were found in these disease categories.

Fumaric aciduria: an overview and the first Brazilian case report

Fumaric aciduria is a rare metabolic disease, with 40 cases reported so far. Fumarase deficiency leads mainly to brain abnormalities, developmental delay, and great accumulation of fumaric acid in urine. This work presents the first case of fumaric aciduria described in Brazil, which presented with some interesting clinical and biochemical findings such as colpocephaly, hepatic alterations, and marked metabolic acidosis since birth. Common findings were ventriculomegaly, hypotonia, and microcephaly. Biochemically, besides the high urinary fumaric acid excretion, atypical elevation of plasma citrulline, tyrosine and methionine levels were also observed. In order to show all features and variants of fumaric aciduria, literature data of 40 patients was reviewed and compared with the case reported here. Findings in all these patients demonstrate that this disorder does not yet have its phenotype completely defined; it is important that more patients be described.

Severe phenotype in MPS II patients associated with a large deletion including contiguous genes

Hunter disease or mucopolysaccharidosis type II (MPS II) is an X‐linked recessive lysosomal disorder caused by the deficiency of iduronate‐2‐sulfatase, which is involved in the catabolism of the glycosaminoglycans (GAGs) heparan and dermatan sulphate. Our aim was to analyze three patients with severe Hunter syndrome that showed a total deletion of the iduronate‐2‐sulphatase (IDS) gene, after exon by exon PCR. DNA was used as a template for PCR synthesis of IDS, FRAXA, FRAXE, and DXS1113 specific amplicons. The DNA analysis for all three patients demonstrated a complete deletion of IDS, FRAXA, and FRAXE contiguous genes. We further performed SNP‐array to delineate the deletion breakpoints and to characterize the deletion extension in the different patients. The results indicated a ∼9.4 Mb deletion in Patient 1, a ∼3.9 Mb deletion of the Xq27.3–Xq28 and a ∼3.1 Mb duplication of the X q28 region in Patient 2 and a ∼41.8 Kb deletion in Patient 3. SNP‐array was shown to be important to map for deletion breakpoints. A comprehensive molecular analysis in patients with Hunter syndrome, especially in the ones presenting the severe form, is important to the understanding of the genetic determinants of the phenotype and for the genetic counseling to be provided to the families.

Hyperargininaemia : A late-diagnosed brazilian case with increased urinary excretion of homocystine

Hyperargininaemia: A late-diagnosed Brazilian case with increased urinary excretion of homocystine R. E. Simoni1, C. P. Honório de Oliveira1, M. J. Braga1, C. R. Gayer de Menezes1, J. C. Llerena Jr2, P. S. Correia2, A. A. Santa Rosa2, D. G. Horovitz2, C. R. M. Chaves2, M. L. Corta de Oliveira1* 1Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janerio, 2Instituto Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil *Correspondence: Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Cidade Universitária, Ilha do Fundão, Centro de Tecnologia, Bloco A, 21941-900, Rio de Janerio, Brazil

Conceptions on genetics in a group of college students

The purpose of this study was to investigate awareness, beliefs, and opinions on genetics in a group of Brazilian college students from several courses. The study used the focus group technique with the participation of 19 students, divided into four groups. Also, it used the isotopic reading technique to analyze the material. The results were divided in four themes: the basic knowledge of genetics, the “new genetics,” including molecular biology and testing, genetic manipulation, and genetics and the media. The participants showed reasonable knowledge on the subject, obtained from various sources, including the printed press, the internet, documentaries, and fictional TV shows. Ethical issues were discussed comprehensively and the groups showed awareness on the hazards brought by genetic reductionism and the need to have some type of regulation regarding genetic manipulation and testing. It is necessary to broaden the debate about the progress in genetics because some of them will affect a significant number of people. This debate should include the lay public, which has been actively participating in decisions involving research and the use of new technologies.

Conhecimento e atitudes sobre genética entre médicos residentes

This article focuses on knowledge, beliefs, and opinions related to genetics among a group of medical residents. Twelve residents in pediatrics, divided into four focus groups, were interviewed during their first month of residency. The material was analyzed using the isotopic reading technique. Participants showed little interest in the topic, despite having a reasonably good level of knowledge, which bore little relationship to their clinical practice, suggesting the need to reformulate medical education. The groups were aware of the high prevalence and morbidity of genetic disorders, thus signaling that the new generation of physicians may be more sensitive to the need to include medical genetics in public health. Brazil is currently experiencing an epidemiological transition, with a proportional increase in genetic disorders as a cause of morbidity and mortality, thus requiring such inclusion in public health planning.

A Survey on Inborn Errors of Metabolism in 323 Neonates from the State of Rio de Janeiro, Brazil

Inborn errors of metabolism (IEM) are a relevant cause of morbidity and death among children, and neonates in particular. However, little is known about the prevalence of these disorders in Brazilian newborns. Our laboratory of IEM (LABEIM) at the Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), has been working on the diagnosis of IEM since 1988. Out of 3,300 patients (90% children), screened and evaluated from 1989 to 2,000 because of a high clinical suspicion of having an IEM, 323 (9.8%) were neonates. Patients came from different regions of the state of Rio de Janeiro, in which lives approximately 8.5% of the total Brazilian population. Chemical tests, various chromatographic techniques and enzyme assays were performed in urine, plasma and in some cases, cerebrospinal fluid (CSF). This study describes our laboratory and the experience with the 323 investigated neonates, among which 28 cases (8.7%) of IEM were identified and 18 (5.6%), strongly suspected. All these cases were related mainly to the metabolism of amino acids, organic acids, lysosomal enzymes and carbohydrates. Furthermore, data on population, community and health services are presented.

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

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.