Clinical Profile Among Brazilian Mucopolysaccharidosis type II Patients: Subgroup Analysis from the Hunter Outcome Survey

Abstract Mucopolysaccharidosis type II (MPS II) is a rare genetic, multiorgan disease. Little information about the Brazilian context is available to date; thus, this descriptive subgroup analysis was conducted on Brazilian data from the Hunter Outcome Survey (HOS), including clinical characteristics among MPS II patients from Brazil. HOS is a global, multi-center, long-term, observational registry of patients with MPS II (NCT03292887). Variables related to organ system involvement, signs and symptoms, surgical procedures and survival among Brazilian patients were extracted from HOS database. Data from 153 Brazilian patients with MPS II were analyzed. Musculoskeletal (96.6%), abdomen/gastrointestinal (95.2%), neurological (88.7%), pulmonary (86.2%), and ear (81.3%) were the most frequently observed organ/systems involved. Regarding signs and symptoms, the most prevalent symptom was coarse facial features consistent with the disease (94.6%), followed by joint stiffness and limited function (89.3%), hernia (84.2%) and hepatomegaly (82.2%). Median survival time was 22.0 years, and the major cause of death was respiratory failure (31.8%). These data may be helpful to understand disease characteristics and to help improve the quality of MPS II patient care in Brazil.

Spinal cord occupation ratio (SCOR) and its application in the diagnosis of cervical spinal cord compression in Mucopolysaccharidoses

Abstract Introduction Mucopolysaccharidoses (MPS) can lead to cervical spinal cord compression (SCC). Diagnostic scores for SCC in MPS use the obliteration of the passage of cerebrospinal fluid in the anterior and posterior spinal cord in the sagittal section of magnetic resonance imaging (MRI). The spinal cord occupation ratio (SCOR) published, by Nouri et al (2018), establishes the spinal cord filling index for the spinal cord, identifying disproportionate spinal cord occupation in the canal. When evaluating congenital canal stenosis, the risk of spinal cord injury has been considered increased when the SCOR is ≥70% in the median sagittal plane or ≥ 80% in the axial plane. Although these values ​​have not been validated for MPS populations, they could be useful. Objective To verify the SCOR in MPS patients with diagnosis of cervical SCC comparing the SCOR with other markers proposed in the existing MPS SCC scores, such as the extent of gliosis, clinical impact and the SCC assessment as represented by the obliteration of CSF flow. Methods We reviewed imaging tests of the cervical spine from MPS patients with previously confirmed SCC, using the SCOR measure in the median sagittal plane, evaluation of the presence and extent of spinal gliosis on MRI, evaluation of the clinical impact using a clinical score and evaluation of the images for the obliteration of cerebral spinal fluid (CSF) flow. Results Thirty-one MRI of 24 different patients were included. The average SCOR was 87.1%. This was lower (81.6%) in patients without gliosis, when compared to those with focal (90.5%) and extensive (97%) gliosis. The only patient with gliosis associated with a lacunar lesion, resulting from an acute compressive injury, had a 68% SCOR, due to the atrophic spinal cord injury. As expected, SCOR was higher in patients with total or partial CSF obliteration, but one among the 3 patients without CSF flow obliteration, with a 76% SCOR, had already developed focal gliosis and mild clinical abnormalities. Patients with more extensive gliosis had higher clinical scores. Four patients had more than one imaging scan evaluated. SCOR upward trend showed an annual average increase of 3.8%. Discussion & Conclusions The use of SCOR allows the diagnosis of cervical spinal canal stenosis in an objective way. It is possible that the cut-off values used by Nouri et al in patients with congenital stenosis could be useful to diagnose cervical stenosis in MPS patients, preceding the finding of CSF flow obstruction, presence of gliosis or clinical abnormalities. Furthermore, the use of SCOR may assist in the longitudinal evaluation of disease progression. Better follow-up and timely diagnosis allows for scheduling of surgery at the best clinical moment, minimizing complications.

Síndrome de Cornelia de Lange: análise de uma série de 33 pacientes em um centro de referência / Cornelia de Lange syndrome: analysis of a series of 33 patients in an excellence center

Introdução: A Síndrome de Cornelia de Lange (CdLS) (OMIM: 122470) é uma doença genética rara com quadro clínico e fenótipo variáveis, compreendendo um grupo de doenças denominado coesinopatias. Entre suas principais características: deficiência intelectual (DI), baixa estatura, doença do refluxo gastroesofágico (DRGE), hipertricose, dismorfismos faciais e anomalias em membros superiores. O diagnóstico pode ser dificultado nos quadros atenuados. O objetivo do estudo foi determinar os principais achados clínicos e moleculares em uma série de pacientes com o diagnóstico clínico de CdLS.Métodos: Foram avaliados 33 pacientes com diagnóstico clínico e/ou molecular de CdLS (18 sexo feminino e 15 masculino) com idades entre 1 mês e 43 anos. Aplicou-se um escore clínico visando a categorização dos pacientes baseado em Kline et al. (2018). Esta ferramenta utiliza sinais clínicos para determinar as formas clássicas (n: 23), não clássicas (n: 6) e os casos que, apesar de não se enquadrarem nestas categoriais, também deveriam ser testados molecularmente para a síndrome (n: 4).Resultados: Atraso do desenvolvimento/DI, distúrbios de comportamento, déficit de crescimento e DRGE foram as comorbidades mais prevalentes. Entre as dismorfias: sinofris, micrognatia, narinas antevertidas e comissura labial desviada para baixo. Os achados moleculares nos pacientes submetidos ao sequenciamento completo do exoma revelaram 6 variantes em NIPBL (46%), 2 variantes em SMC1A (15%), 1 variante em SMC3, 1 variante em HDAC8, 1 variante em AHDC1 e 2 resultados negativos.Conclusões: Os dados obtidos revelaram uma grande heterogeneidade de apresentação da síndrome. A utilização de escores clínicos podem auxiliar no diagnóstico de CdLS.

Introduction: Cornelia de Lange syndrome (CdLS) (OMIM: 122470) is a rare genetic disease with variable clinical presentation and phenotype, part of a group of disorders termed cohesinopathies. Intellectual disability, growth retardation, gastroesophageal reflux disease, hypertrichosis, facial dysmorphisms, and anomalies of the upper limbs are the most common clinical characteristics. Diagnosis may be difficult, especially in attenuated presentations. The aim of this study was to determine the main clinical and molecular findings in a series of patients with clinical diagnosis of CdLS.Methods: Thirty-three patients with typical clinical and/or molecular diagnosis of CdLS (18 female and 15 male) aged between 1 month and 43 years were evaluated. A clinical score was applied to categorize patients. This tool uses clinical signs to determine the classic (n: 23) and nonclassic (n: 6) forms, in addition to a category to suggest which cases should be molecularly tested for the syndrome (n: 4).Results: Developmental delay/intellectual disability, behavioral disorders, growth retardation, and gastroesophageal reflux disease were the most prevalent comorbidities. Dysmorphic features included synophrys micrognathia, anteverted nostrils, and labial commissure turning downwards. Molecular findings in those who underwent whole exome sequencing revealed 6 variants in NIPBL (46%), 2 variants in SMC1A (15%), 1 variant in SMC3, 1 variant in HDAC8, 1 variant in AHDC1, and 2 negative results.Conclusions: The data revealed a great heterogeneity in the presentation of the syndrome. The use of clinical scores can help in the diagnosis of CdLS.

Description of Functioning in Children and Adolescents with Mucopolysaccharidosis - Case series

Abstract Introduction: Rare health conditions as mucopolysaccharidoses (MPS) can directly influence functioning experiences. Mobility restriction, osteoarticular alterations, leads to delayed neuropsychomotor development are some of the negative impacts of MPS. Aims: The purpose of this study is to evaluate the functioning of children with MPS, from the International Classification of Functioning, Disability, and Health (ICF) perspective. Methodology: It is a case series study with a sample of 15 children and adolescents with MPS with a median age of 12 years, followed in a tertiary hospital in Rio de Janeiro, Brazil. Results: The patients were assessed by the model ICF and results were as following: regarding body functions, most categories presented slight impairment. For mobility of joints and gait, the impairment was severe. Activity and participation with most significant limitations were "learning to read/write", "read/write", "listening" and "performing multiple tasks." In self-care, the main limitations were in "drinking", "taking care of body parts" and "taking care of one's health." Also, there were restrictions on "doing household tasks", "basic economic transactions", "community living" and "religion and spirituality". Conclusion: MPS can have a significant impact in different body systems which act as limiting activities that require body mobility.

Perthes-Like Disease Masquerading Non-Classical MPS

Abstract Mucopolysaccharidoses (MPS) are inborn errors of metabolism caused by deficient lysosomal enzymes, leading to organomegaly, hip osteonecrosis, coarse facial features, bone deformities, joint stiffness, cardiac and pulmonary symptoms (MPS VI) or hypermobility (MPS IVA). Some patients may present with non-classical forms of the disease in which osteoarticular abnormalities are the initial symptoms of non-classical forms. As orthopedists and surgeons are the specialists most frequently consulted before the diagnosis, it is critical that MPS may be considered as a differential diagnosis for patients with bone dysplasia. Experts in Latin America reviewed medical records focusing on disease onset, first symptoms and the follow-up clinical and surgical outcomes of non-classical MPS VI and IVA patients. All patients displayed orthopedic issues, which worsened over time, followed by cardiac and ophthalmological abnormalities. Our findings enlighten the necessity of including non-classical MPS as possible diagnosis for patients who report osteoarticular abnormalities in absence of inflammation.

Identification of relevant international Classification of Functioning Disability and Health (ICF) categories in patients with 22q11. 2 Deletion Syndrome: a Delphi exercise

ABSTRACT Purpose: The aim of this study was to identify the most typical and relevant categories of the International Classification of Functioning, Disability and Health (ICF) for patients with 22q11.2 Deletion Syndrome. Methods: Based on the Delphi technique an expert survey through e-mail was performed among health professionals' specialists in the 22q11.2DS. Data were collected in 2 rounds. Answers were analysed for the degree of consensus. Results: 7 Experts recruited through e-mail distribution lists of professional organizations and personal networks participated in the study. Categories in all ICF components that were considered typical and/or relevant by at least 80% of the responders were added to a pilot ICF instrument for children with 22q11.2DS, with a total of 145 ICF categories. Conclusion: a list of ICF categories that are considered relevant and typical for 22q11.2DS condition by international experts was created. This is an important step towards identifying ICF Core Sets for chronic paediatric conditions in Brazil.

Adoecimentos raros e o diálogo associativo: ressignificações para experiências morais / Rare diseases and the associative dialogue: resignifications for moral experiences

Resumo Neste artigo, buscamos discutir a experiência de familiares de crianças e adolescentes com doenças raras como uma experiência moral. A experiência moral se caracteriza pelo sofrimento que é lido, coletivamente, como acontecimento catastrófico, mobilizando recursos para significação e sentido que possibilitem reconstruções identitárias, valoração de novas trajetórias a partir de um diagnóstico raro, assim como a busca de pares. Nesse sentido, é fundamental a construção de relações de reconhecimento, alteridade e pertencimento. A partir de uma perspectiva interacionista simbólica, os resultados mostram dois núcleos: (1) o susto como surpresa diante do diagnóstico inesperado, levando a busca de pares e promoção do reconhecimento social; (2) o custo envolvido com a trajetória de uma doença rara que implica um trabalho de care e a aquisição de capital associativo como possibilidade de fortalecimento e construção de capital social de cuidado à saúde.

Abstract This paper aims to discuss the experience of relatives of children and adolescents with rare diseases as a moral experience. Moral experience is characterized by suffering that is socially interpreted as a catastrophic event, mobilizing resources for signification and meaning that allow the reconstruction of identity, the appreciation of itineraries from a rare diagnosis, as well as the search for peers. Thus, the construction of relationships of recognition, alterity, and belonging is fundamental. From a symbolic interactionist perspective, the results show two significant cores: (1) shock as a surprise in the face of an unexpected diagnosis, leading to the search for peers and promotion of social recognition; (2) the cost involved with the course of a rare disease that implies a care work and the acquisition of associative capital as a possibility of strengthening and building the social capital of health care.

Recommendations for Assessment and Management of Health-Related Quality of Life in Patients with Mucopolysaccharidoses in Latin America

Abstract Mucopolysaccharidoses (MPS) constitute a heterogeneous group of rare genetic disorders caused by enzymatic deficiencies that lead to the accumulation of glycosaminoglycans (GAGs). Clinical observations suggest a health-related impairment in quality of life in patients with MPS. Professionals with extensive experience in the care of patients with inborn errors of metabolism, such as MPS, held a meeting in April 2017 to discuss and propose recommendations for the evaluation and management of quality of life in MPS patients in Latin America. In the light of this scenario, the present work summarizes the content of the discussions and presents the recommendations produced at the meeting. The panel had suggested the use of the following tools for the assessment of health-related quality of life (HRQoL): Children's Health Assessment Questionnaire (CHAQ) for children and patients unable to express their feelings, Health Assessments Questionnaire (HAQ) and EuroQol 5 Domains (EQ-5D) scales for adult patients. Based on the scores verified in these scales, the panel proposes interventions that aim reducing the impairment of the quality of life in patients with MPS disorders.

Cuidado complexo, custo elevado e perda de renda: o que não é raro para as famílias de crianças e adolescentes com condições de saúde raras / Complex care, high cost, and loss of income: frequent issues for families of children and adolescents with rare health conditions / Cuidado complejo, costo elevado y pérdida de renta: lo que no es raro para las familias de niños y adolescentes que sufren problemas de salud raros

Resumo: Estimativas apontam que há mais de 7 mil doenças raras já identificadas, que representam de 6 a 10% de todas as doenças no mundo. No Brasil, considera-se doença rara aquela que afeta até 65 pessoas em cada 100 mil indivíduos. Quantificar os custos para as famílias de pacientes com essas condições e o seu comprometimento sobre a renda fornece informações capazes de apoiar as políticas públicas destinadas a esses pacientes. O objetivo deste estudo foi estimar o custo e a perda de renda sob a perspectiva das famílias de crianças e adolescentes com fibrose cística, mucopolissacaridoses e osteogênese imperfeita. Foi realizado com 99 famílias de pacientes atendidos em um hospital de referência nacional em doenças raras no Rio de Janeiro, mediante relato do cuidador principal. A análise descritiva dos dados mostrou que o custo mediano direto não médico para as famílias foi de R$ 2.156,56 para fibrose cística, R$ 1.060,00 para mucopolissacaridoses e R$ 1.908,00 para osteogênese imperfeita. A perda de renda superou 100% para as três condições analisadas. Um total de 54% das famílias não recebem benefícios assistenciais. A estimativa de coping costs indicou que 69% das famílias acessaram empréstimos e 22,5% venderam bens para lidar com os custos do curso do tratamento. Foram verificados gastos catastróficos para as famílias das três doenças analisadas. Os resultados trazem à tona um tema que descortina custos pouco estimados, não somente no campo das doenças raras. São resultados que indicam uma carga importante sobre a renda das famílias. É importante incorporar estudos de tal natureza na discussão do financiamento, da incorporação de novas tecnologias e da oferta de serviços de saúde.

Abstract: Estimates point to more than seven thousand rare diseases already identified, representing 6 to 10% of all diseases. In Brazil, a rare disease is defined as one that affects up to 65 persons per 100,000. The quantification of costs for the families of patients with such conditions and their impact on income provides information capable of supporting public policies for these youngsters. The study aimed to estimate the cost and loss of earnings, viewed from the perspective of families of children and adolescents with cystic fibrosis, mucopolysaccharidosis, and osteogenesis imperfecta. The study included 99 families of patients treated at a national referral hospital for rare diseases in Rio de Janeiro, based on the principal caregiver's report. The descriptive data analysis showed that the median direct nonmedical cost for families was BRL 2,156.56 (USD 570) for cystic fibrosis, BRL 1,060.00 (USD 280) for mucopolysaccharidosis, and BRL 1,908.00 (USD 505) for osteogenesis imperfecta. Loss of earnings exceeded 100% for all three diseases. A total of 54% of families fail to receive any social benefits. The estimate of coping costs indicated that 69% of the families had incurred loans and that 22.5% had sold household assets to cope with the treatment costs. Catastrophic expenditures were observed in families dealing with the three diseases. The results unveil costs that are rarely estimated, and not only in the field of rare diseases. The findings point to a major burden on the families' income. It is important to incorporate such studies in the discussion of financing, the incorporation of new technologies, and the supply of health services.

Resumen: Las estimaciones apuntan que hay más de 7 mil enfermedades raras ya identificadas, que representan de un 6 a un 10% de todas las enfermedades en el mundo. En Brasil, se considera enfermedad rara a aquella que afecta hasta a 65 personas por cada 100 mil individuos. Cuantificar los costos para las familias de pacientes que las sufren, y el peso económico que representan para la renta familiar, proporciona información capaz de apoyar políticas públicas destinadas a estos pacientes. El objetivo de este estudio fue estimar el coste y la pérdida de renta desde la perspectiva de las familias de niños y adolescentes con fibrosis cística, mucopolisacaridosis y osteogénesis imperfecta. Se realizó con 99 familias de pacientes atendidos en un hospital de referencia nacional en enfermedades raras en Río de Janeiro, a través del relato del cuidador principal. El análisis descriptivo de los datos mostró que el coste medio directo no-médico para las familias fue de BRL 2.156,56 en la fibrosis cística, BRL 1.060,00 en la mucopolisacaridosis y BRL 1.908,00 en la osteogénesis imperfecta. La pérdida de renta superó el 100% en las tres condiciones analizadas. Un total de un 54% de las familias no recibe beneficios asistenciales. La estimativa de coping costs indicó que un 69% de las familias accedieron a préstamos y un 22,5% vendieron bienes para lidiar con los costos del tratamiento en curso. Se observaron gastos catastróficos para las familias de las tres enfermedades analizadas. Los resultados traen a colación un tema que desvela costos poco estimados, no solamente en el campo de las enfermedades raras. Son resultados que indican una carga importante sobre la renta de las familias. Es importante incorporar estudios de esta naturaleza en la discusión sobre la financiación, incorporación de nuevas tecnologías y oferta de servicios de salud.

Hematopoietic Stem Cell Transplantation in Mucopolysaccharidosis Type II: A Literature Review and Critical Analysis

Abstract Mucopolysaccharidosis II (MPS II—Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency in iduronate-2 sulfatase. Enzyme replacement therapy does not cross the blood-brain barrier (BBB), limiting the results in neurological forms of the disease. Another treatment option for MPS, hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for the severe form of MPS I since it can preserve neurocognition when performed early in the course of the disease. Even though the intravenous therapy does not cross the BBB, it has become the recommended treatment for MPS II, and HSCT was not often indicated. In an attempt to understand why this treatment modality is rejected by most specialists as a treatment option for patients with Hunter syndrome, we sought to raise all HSCT cases already reported in the scientific literature. Databases used were Medline/PubMed, Lilacs/BVS Cochrane Library, DARE, SciELO, and SCOPUS. Different combinations of the terms "mucopolysaccharidosis II," "Hunter syndrome," "hematopoietic stem cell transplantation," "bone marrow transplantation," and "umbilical cord blood stem cell transplantation" were used. A total of 780 articles were found. After excluding redundant references and articles not related to the theme, 26 articles were included. A descriptive summary of each article is presented, and the main features are summed up. The clinical experience with HSCT in MPS II is small, and most of the available literature is outdated. The available data reveal poor patient selection criteria, varied conditioning regimens, distinct follow-up parameters, and post-HSCT outcomes of interest, making impossible to compare and generalize the results obtained. Recently, after the development of new conditioning protocols and techniques and the creation of bone marrow donor registries and umbilical cord banks, HSCT has become more secure and accessible. It seems now appropriate to reconsider HSCT as a treatment option for the neuronopathic form of MPS II.

Redes de tratamento e as associações de pacientes com doenças raras / Treatment networks and associations of patients with rare diseases

Resumo As associações de pacientes são um exemplo de grupos biossociais, já que sua constituição é motivada por questões biológicas comuns, tais como as doenças raras, e estão, por vezes, inscritas no movimento social em saúde. Apesar da Política Nacional de Atenção Integral às Pessoas com Doenças Raras ter sido promulgada em 2014, os pacientes ainda têm dificuldade em garantir acesso a tratamento pelo Sistema Único de Saúde. Investigamos como as associações de pacientes com doenças raras tecem, através das redes sociais virtuais, o acesso a tratamento. Esta pesquisa é parte de um estudo sobre o uso das mídias sociais pelas associações de pacientes com doenças raras, e emprega como método a netnografia. As fontes da pesquisa foram páginas de associações de pacientes com doenças raras no Brasil presentes no Facebook. Observamos que a atuação das associações de pacientes é plural, indo desde a orientação de pacientes e familiares sobre questões relacionadas a tratamento e qualidade de vida, até a participação ativa na elaboração e implementação de políticas públicas. Os discursos sugerem que o foco destas associações é, na maior parte dos casos, o acesso a medicamentos, em detrimento da implantação efetiva da Política Nacional de Atenção Integral às Pessoas com Doenças Raras.

Abstract Patients' associations are an example of biosocial groups, since their formation is motivated by common biological characteristics, such as rare diseases, and they are sometimes included in social movements in health. Even though the National Policy on Comprehensive Care for Persons with Rare Diseases was enacted in 2014, patients still struggle to ensure access to and treatment by the Unified Health System. The way in which associations of patients with rare diseases gain access to treatment via social networks, is investigated. This research is part of a study about the use of social media by associations of patients with rare diseases, which employs netnography - ethnography applied to the web - as the data-gathering method. Data sources were pages of the associations on Facebook in Brazil. It was seen that the activities of the associations are multi-faceted, ranging from patient and family guidance about treatment and quality of life, to active participation in the elaboration and implementation of public policies. The discourses suggest that the focus of patients' associations is, in the majority of cases, the access to drugs rather than the effective enactment of the national policy geared towards rare diseases.

Respiratory manifestations in late-onset Pompe disease: a case series conducted in Brazil / Manifestações respiratórias na doença de Pompe de início tardio: uma série de casos no Brasil

ABSTRACT Objective: To describe respiratory function in a series of patients with late-onset Pompe disease after the definitive diagnosis and before enzyme replacement therapy. Methods: This was a cross-sectional study involving patients with a definitive molecular diagnosis of late-onset Pompe disease. The data analyzed included age at symptom onset; age at definitive diagnosis; type of initial symptoms; time from symptom onset to diagnosis; FVC in the sitting and supine positions; six-minute walk distance; and locomotor ability. Analyses were carried out using frequencies, medians, minimum values, and maximum values. Results: Six patients were included in the study. The median age at symptom onset was 15 years (range, 13-50 years), and the median age at diagnosis was 39.5 years (range, 10-64 years). The median time from symptom onset to diagnosis was 8 years (range, 0-45 years). In all cases, the initial manifestation of the disease had been motor weakness. The median FVC in percentage of the predicted value (FVC%) in the sitting and supine positions was 71.0% (range, 22.9-104.6%) and 58.0% (range, 10.9-106.9%), respectively. The median ΔFVC% was 24.5% (range, −4.59 to 52.40%).The median six-minute walk distance was 391.7 m (range, 97-702 m) . Conclusions: In this case series, the time from symptom onset to diagnosis was long. Although respiratory signs or symptoms were not the initial manifestations of the disease, 66.7% of the patients showed reduced FVC% in the sitting and supine positions at diagnosis.

RESUMO Objetivo: Descrever a função respiratória em uma série de pacientes com doença de Pompe de início tardio após o diagnóstico definitivo e antes do início do tratamento através de terapia de reposição enzimática. Métodos: Estudo transversal em pacientes com diagnóstico molecular de doença de Pompe de início tardio. As informações analisadas incluíram idade ao início dos sintomas e ao diagnóstico, tipo de sintoma inicial, tempo entre início dos sintomas e diagnóstico, CVF em posição sentada e supina, distância percorrida no teste de caminhada de seis minutos e capacidade de locomoção. Análises por frequência, mediana, valor mínimo e valor máximo foram realizadas. Resultados: Foram incluídos seis pacientes no estudo. A mediana de idade ao início dos sintomas foi de 15 anos (variação, 13-50 anos) e a de idade ao diagnóstico foi de 39,5 anos (variação, 10-63 anos). A mediana de tempo entre o início dos sintomas e a confirmação diagnóstica foi de 8 anos (variação, 0-45 anos). A manifestação inicial da doença foi de sintomas motores de fraqueza muscular em todos os casos. As medianas da CVF em porcentagem do previsto (CVF%) em posição sentada, em supino e ΔCVF% foram de, respectivamente, 71,0% (variação, 22,9-104,6%), 58,0% (variação, 10,9-106,9%) e 24,5% (−4,59 a 52,40%). A mediana da distância percorrida no teste de caminhada de seis minutos foi de 391,7 m (variação, 97-702 m) . Conclusões: Nesta série, o tempo entre o início dos sintomas e o diagnóstico foi longo. A manifestação inicial da doença não foi de sinais ou sintomas respiratórios, embora 66,7% dos pacientes apresentassem redução da CVF% em posição sentada e em supino no momento do diagnóstico.

Contradicoes das politicas publicas voltadas para doencas raras: o exemplo do Programa de Tratamento da Osteogenese Imperfeita no SUS / Contradictions of public health policies geared to rare disorders: the example of the Osteogenesis Imperfecta Treatment Program in the Brazilian Unified Health System (SUS)

O artigo visa discutir o processo de consolidação de uma política pública, no Brasil, voltada a uma doença rara - a osteogênese imperfeita, cujo tratamento passou a responsabilidade do SUS em 2001 através da Portaria GM/MS2305/2001. O processo de implementação desta terapia vem sendo acompanhado de contradições, sobretudo no que diz respeito às decisões terapêuticas e ao fortalecimento da rede especializada na abordagem desta condição, atitudes claramente percebidas tanto no processo de elaboração quanto no texto da nova Portaria 714/2010.

The scope of this paper is to examine the process of consolidation of a public health policy in Brazil geared to a rare disorder, namely osteogenesis imperfecta, the treatment for which has fallen under the responsibility of the Brazilian Unified Health System (SUS) after the publication of Ministerial Ruling GM/MS2305/2001. The implementation of this law has been accompanied by many contradictions, especially with respect to therapeutic decisions and the strengthening of the specialized network for addressing this condition. These attitudes are clearly shown both by the drafting process and the final text of the new law (Ministerial Ruling 714/2010).

Atenção em genética médica no sus: a experiência de um município de médio porte / Attention in medical genetics in the brazilian health system: the experience of a medium-sized municipality

Realizou-se estudo descritivo e exploratório da experiência em município de médio porte da implantação de ações na área da Genética, conjugando a análise dos documentos oficiais e de um questionário aplicado a 43 profissionais de nível superior da Estratégia Saúde da Família. Os dados obtidos foram analisados buscando obter respostas sobre como e por que foram realizadas determinadas estratégias de atenção à saúde na área da Genética Clínica e Comunitária. Tais ações foram classificadas em "educação permanente", "vigilância em saúde" e "ampliação do acesso à assistência". Os resultados revelaram que ainda é necessário estender as ações de educação permanente na área para profissionais da atenção primária, possibilitando assim promover a efetivação dessa porta de entrada do Sistema Único de Saúde para a área da Genética e o acesso a um cuidado integral em saúde.

We conducted a descriptive study on the experience of implementation of actions in the area of genetics in a medium-sized municipality, combining the analysis of official documents and a questionnaire administered to 43 university level professionals of the Family Health Strategy. The data were analyzed looking for answers about how and why certain health care strategies in the area of clinical and community genetics were performed. Such actions were classified as "continuing education", "health surveillance" and "enhanced access to care". The results showed that it is still necessary to extend the actions of continuing education in genetics for primary care professionals, promoting this gateway to the SUS also to the area of genetics, in order to allow full access to comprehensive health care.

Avaliação genética itinerante de crianças e adolescentes com deficiência vinculadas à Estratégia Saúde da Família / Genetic evaluation as an itinerant strategic medical care towards impaired children and teenagers in the Brazilian Family Health Program / Evaluación genética itinerante de niños y adolescentes con deficiencia relacionados a la estrategia Brasileña de Salud Familiar

As doenças genéticas atingem cerca de 3% a 10% da população e podem levar a problemas de saúde crônicos e deficiências. O objetivo deste trabalho foi descrever uma experiência nacional inédita de assistência na área da genética clínica por meio de uma equipe itinerante de especialistas que avaliou pacientes selecionados pela atenção primária a partir da ficha complementar de cadastro de pessoas com deficiências. Foi realizado estudo descritivo e transversal dos pacientes identificados a partir da ficha complementar de cadastro de pessoas com deficiências, avaliados pela equipe em 2005, 2008 e 2009, num total de 324 famílias. A etiologia da deficiência foi definida como genética em 38% dos casos e ambiental em 32,7%. A prevalência de malformações congênitas foi de 31,8%. A utilização da ESF como porta de entrada ampliou o acesso a serviços de alta complexidade para pessoas com doenças de origem genética, defeitos congênitos e deficiências. Os resultados expõem a necessidade de interiorização da genética médica e suas interfaces com a atenção primária, reforçando a importância da implementação de políticas de saúde nesta área.

Genetic disorders affect about 3-10% of the population and can lead to chronic health problems and disabilities. The present work aimed to describe a new experience in health care in clinical genetics by an itinerant team of experts that evaluated patients selected by the primary care through the supplementary registration form for people with disabilities. A descriptive and transversal study was carried out with patients, who were previously identified by the supplementary registration form for people with disabilities, evaluated by the team in 2005, 2008 and 2009, in a total of 324 families. The etiology of disability was defined as genetic in 38% of the cases and environmental in 32.7%. The prevalence of congenital malformations was 31.8%. Family Health Strategy was utilized as a gateway to expand the access to health services for people with highly complex genetic diseases, birth defects and disabilities. The results expose the need to interiorize medical genetics and its interfaces with primary care in Brazil, reinforcing the importance of implementing health policies in this area.

Las enfermedades genéticas alcanzan a cerca del 3 a 10% de la población y pueden llevar a problemas crónicos de salud y deficiencias. El objetivo deste trabajo fue describir una experiencia nacional inédita de asistencia en el área de la genética clinica por medio de un equipo itinerante de especialistas que evaluaron pacientes seleccionados por la atención primaria a partir de la historia clínica disponible en el registro de personas con deficiencia. Fue realizado un estudio descriptivo y transversal de los pacientes identificados a partir de la historia clínica disponible en el registro de personas con deficiencia en 2005, 2008 y 2009, con un total de 324 familias. La etiologia de deficiencia fue definida como genética en 38% y ambiental en 32,7% de los casos. La prevalencia de malformaciones congénitas fue de 31,8%. La utilizacion de Estrategia de Salud Familiar como puerta de entrada amplió el acceso a servicios de alta complejidad para personas con enfermedades de origen genético, defectos congénitos y deficiencias. Nuestros resultados exponen la necesidad de interiorización de la genética médica y sus interfaces con la atencion primaria de la salud, reforzando la importância de implementar políticas de salud en esa área.

Conhecimento e atitudes sobre genética entre médicos residentes / Knowledge and attitudes on genetics among a group of medical residents

O objetivo deste trabalho foi estudar o conhecimento, as crenças e opiniões sobre Genética em um grupo de médicos residentes. Foi utilizada a técnica de grupos focais com 12 residentes de Pediatria em seu primeiro mês de curso, divididos em quatro grupos. Para a análise do material, foi escolhida a técnica da leitura isotópica. Os participantes demonstraram pouco interesse pelo assunto, mas tinham um grau razoável de conhecimento. Este conhecimento, entretanto, era pouco vinculado à prática clínica, sugerindo a necessidade de reformulação da formação médica. Os grupos mostraram consciência da alta prevalência e da grande morbidade das doenças genéticas, sinalizando que a nova geração de médicos pode ser mais sensível à questão da inserção da Genética na saúde pública. O Brasil está passando por um momento de transição epidemiológica, com o aumento proporcional das doenças de etiologia genética como causas de morbi-mortalidade, tornando necessária a inclusão dessas condições no planejamento para a gestão da saúde pública.

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.

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

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.

Terapia de reposição enzimática para as mucopolissacaridoses I, II e VI: recomendações de um grupo de especialistas brasileiros / Enzyme replacement therapy for mucopolysaccharidoses I, II and VI: recommendations from a group of Brazilian F experts

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...

Atenção aos defeitos congênitos no Brasil: características do atendimento e propostas para formulação de políticas públicas em genética clínica / Birth defects in Brazil and health care: proposals for public policies in clinical genetics

O impacto dos defeitos congênitos no Brasil vem aumentando, apontando para a necessidade de estratégias específicas na política de saúde. Apesar da íntima ligação da genética clínica com a atenção aos defeitos congênitos, menos de 30 por cento da demanda vem sendo absorvida pelos serviços do país. São problemas na atenção aos defeitos congênitos: dificuldades de acesso aos serviços de genética com concentração destes no Sul/Sudeste e suporte laboratorial insuficiente. Para melhor abordagem aos defeitos congênitos, ações para o estabelecimento de política em genética clínica deveriam ser deflagradas, preferencialmente sob coordenação de grupo técnico vinculado ao Ministério da Saúde, tendo como objetivo organizar rede clínico-laboratorial na especialidade. Ações visando à otimização de recursos e ao aumento da cobertura deverão ser consideradas. Para suporte laboratorial são prementes arranjos visando o fluxo de exames e criação de mecanismos de financiamento. Ações complementares de prevenção e registro epidemiológico dos defeitos congênitos, educação médica e do usuário são recomendadas. Com tais propostas contempladas, será possível a estruturação de uma rede regionalizada, hierarquizada e funcional, além de mais justa e mais democrática, voltada à atenção aos defeitos congênitos no Brasil.

The impact of birth defects in Brazil has increased steadily, indicating the need for specific health policy strategies. Despite the close relationship between clinical genetics and management of birth defects, less than 30 percent of the total demand is currently met by existing genetic services. The main problems are: difficult access to genetic services, services highly concentrated in the South and Southeast regions of the country, and insufficient laboratory support. With the aim of improving management of birth defects, a specific national policy coordinated by the Ministry of Health needs to be developed. The main goal of such a policy should be the organization of a functional integrated genetics network, in addition to rational use of resources and enhanced coverage. In order to formalize a national laboratory network, sample shipping and billing mechanisms must be created. Birth defect prevention, education for the medical community and general population, and solid epidemiological data collection are strongly recommended as complementary measures. If such recommendations are implemented, it could be possible to organize a network for management of birth defects in Brazil that is regionalized, hierarchical, functional, and democratic as well.

Atenção aos defeitos congênitos no Brasil: panorama atual / Birth defects and health strategies in Brazil: an overview

O impacto dos defeitos congênitos no Brasil vem aumentando progressivamente, tendo passado da quinta para a segunda causa dos óbitos em menores de um ano entre 1980 e 2000, apontando para a necessidade de estratégias específicas na política de saúde. Foram localizadas, no Brasil, direcionadas aos defeitos congênitos, ações governamentais e não-governamentais. Estas envolvem serviços de informação sobre agentes teratogênicos na gravidez e sobre doenças metabólicas geneticamente determinadas, monitorização de defeitos congênitos, programa de triagem neonatal e tratamento de algumas doenças genéticas, imunização contra rubéola, além da fortificação de farinhas com ácido fólico como ação preventiva de certos defeitos congênitos. Apesar da importância de tais iniciativas, é pouco provável que seja possível atender à questão dos defeitos congênitos de forma integrada. Para a efetivação de um sistema de atenção voltado aos defeitos congênitos, deverá ser formulada política específica, de âmbito nacional, com a participação ativa do Ministério da Saúde, utilizando, como espinha dorsal, os serviços de genética existentes. Só assim, será possível a estruturação de uma rede regionalizada, hierarquizada e funcional voltada à atenção aos defeitos congênitos no Brasil.