ABSTRACT
BACKGROUND: Hemicrania continua is a rare form of cephalalgia featuring a chronic and persistent headache in only one side of the head. OBJECTIVES: In this report, we present a case of a patient with hemicrania continua and systemic lupus erythematosus (SLE). METHODS: We collected patient data through the electronic medical record. Afterward, we reviewed the literature regarding hemicrania continua and its pathophysiology and correlation with neurovascular alterations, inflammation, and SLE. RESULTS: A 42-year-old woman visited the emergency department due to worsening constant unilateral cephalalgia that had been present for the past 6 months. The patient reported a highly intense (10/10) headache in the entire left hemicrania that radiated to the left shoulder. During physical examination, she presented with nystagmus, vertigo, and aggravated cephalalgia associated to body movement and, despite having no optic nerve thickening. In addition, she had jaundice, tachycardia, and splenomegaly. Complimentary exams found deep anemia, depletion in complement system and anti-nuclear factors, suggesting a possible hemolytic anemia (AIHA) due to SLE. Treatment was initiated with hydrocortisone and prednisone, associated with amitriptyline, fluoxetine and diazepam, reaching full remission. CONCLUSION: These syndromes have aggravated each other, and possibly the explanation for the cephalalgia remission was the control of AIHA and SLE. It features a rare case in literature and thus warrants discussion.
INTRODUÇÃO: Hemicrania contínua é uma forma rara de cefaléia caracterizada por cefaleia crônica e persistente em apenas um lado da cabeça. OBJETIVOS: Neste relato apresentamos o caso de um paciente com hemicrania contínua e lúpus eritematoso sistêmico (LES). MÉTODOS: Coletamos dados dos pacientes por meio do prontuário eletrônico. Posteriormente, revisamos a literatura sobre a hemicrania contínua e sua fisiopatologia e correlação com alterações neurovasculares, inflamação e LES. RESULTADOS: Uma mulher de 42 anos recorreu ao serviço de urgência devido ao agravamento da cefaleia unilateral constante, presente nos últimos 6 meses. O paciente relatou cefaleia de alta intensidade (10/10) em toda a hemicrânia esquerda com irradiação para o ombro esquerdo. Ao exame físico apresentava nistagmo, vertigem e cefaléia agravada associada à movimentação corporal e, apesar de não apresentar espessamento do nervo óptico. Além disso, ela apresentava icterícia, taquicardia e esplenomegalia. Os exames complementares evidenciaram anemia profunda, depleção do sistema complemento e fatores antinucleares, sugerindo uma possível anemia hemolítica (AIHA) por LES. Iniciou-se tratamento com hidrocortisona e prednisona, associadas a amitriptilina, fluoxetina e diazepam, atingindo remissão completa. CONCLUSÃO: Essas síndromes agravaram-se mutuamente e possivelmente a explicação para a remissão da cefaléia foi o controle da AIHA e do LES. Apresenta um caso raro na literatura e, portanto, merece discussão.
Subject(s)
Humans , Headache Disorders/complications , Headache/complications , Rare Diseases/complicationsABSTRACT
A Avaliação de Tecnologias em Saúde (ATS) considera os domínios de benefícios clínicos, perfil epidemiológico, inovação, custo-efetividade, ética e de equidade no processo de decisão dos gestores em saúde. No contexto dos medicamentos para doenças raras, é desafiador o trabalho da ATS, dada a baixa disponibilidade de evidências robustas e o alto custo unitário das tecnologias. O objetivo da revisão foi analisar as estratégias disponíveis de avaliação das demandas de incorporação de medicamentos para o tratamento de doenças raras em sistemas de saúde. Foi realizada uma revisão rápida com busca estruturada na base de dados MEDLINE (via PubMed), Cochrane Library e Health Systems Evidence. Incluíram-se estudos sobre estratégias de avaliação de medicamentos utilizados para tratamento de doenças raras. Adicionalmente, foram realizadas buscas nas Agências de ATS do Brasil, Austrália, Nova Zelândia, Canadá, Reino Unido, França, Estados Unidos e Alemanha. A síntese dos resultados foi qualitativa com o agrupamento dos achados nos seguintes eixos temáticos: Segurança e efetividade, Custo-efetividade, Impacto orçamentário e Perspectiva da sociedade. Foram identificadas 267 publicações, sendo selecionadas 16 das bases de dados indexadas e 7 da literatura cinzenta. Com a análise dos documentos, pode-se concluir que a adoção de critérios específicos harmonizada com o atual modelo de ATS é um possível caminho a ser seguido no contexto dos medicamentos para doenças raras. Concomitante a isso, abordagens no sentido de incentivo a pesquisa e produção de dados de mundo real e a criação de comitês específicos para tratativa do tema nas agências de ATS apresentam-se como alternativa para lidar com as fragilidades no contexto de doenças raras.
The Health Technology Assessment (HTA) considers evidence regarding clinical benefits, epidemiological profile, innovation, cost-effectiveness, ethics and equity in its assessment process to support managers' decisions. In the context of drugs in rare diseases, the work of the ATS is challenging given the low availability of evidence and the high cost of technologies. The objective of the review was to analyze the available strategies for evaluating the demands for incorporating drugs for the treatment of rare diseases in health systems. A rapid review was performed with a structured search in the MEDLINE database (via PubMed), the Cochrane Library and Health Systems Evidence. Studies on strategies for evaluating drugs used to treat rare diseases were included and, additionally, searches were carried out in ATS Agencies in Brazil, Australia, New Zealand, Canada, United Kingdom, France, United States and Germany. The synthesis of the results was qualitative, grouping the major ones into thematic axes: Safety and effectiveness, Cost-effectiveness, Budgetary impact and Society's perspective. 267 publications were identified, 16 selected from indexed databases and 7 from gray literature. With the analysis of the documents, it can be concluded that the adoption of specific criteria harmonized with the current ATS model is a possible path to be followed in the context of drugs for rare diseases. At the same time, approaches to encourage research and the creation of specific committees to deal with the issue in HTA agencies would complement actions towards the consolidation of this work.
Subject(s)
Orphan Drug Production , Technology Assessment, Biomedical , Rare DiseasesABSTRACT
Patients with rare diseases frequently face unmet medical needs due to the high costs, lengthy development times, and slow approval processes for new treatments. This case study discusses innovative access alternatives for rare diseases in Brazil, focusing on early access to pabinafusp-alfa for mucopolysaccharidosis type II (MPS-II), a rare genetic lysosomal storage disease characterized by a deficiency of the enzyme iduronate-2-sulfatase. From September 2018 to March 2023, 20 Brazilian MPS-II patients received pabinafusp-alfa through a clinical research protocol. This enzyme replacement therapy (ERT) crosses the blood-brain barrier to address central nervous system manifestations unmet by existing treatments. Patients' participation in the clinical study resulted in an estimated BRL 65 million in cost savings for the public healthcare system compared to conventional ERT with idursulfase-alfa and potentially better clinical outcomes. The case study underscores the importance of innovative mechanisms in addressing patients' medical needs. Early access alternatives include: a) clinical study access, with execution/development aligned with healthcare managers and linked to future access strategies; b) regulatory-level risk-sharing, considering effectiveness uncertainties and the possibility of market withdrawal and/or reimbursement in case of negative results; and c) drug pre-delivery, with payment contingent on positive phase III clinical study outcomes. Although public-private partnerships in clinical research are underused, they could benefit all stakeholders by accelerating drug development, facilitating early patient access to innovative medicines, and generating healthcare system savings, particularly for rare diseases.
Pacientes com doenças raras frequentemente enfrentam necessidades médicas não atendidas devido aos altos custos, longos tempos de desenvolvimento e processos de aprovação lentos para novos tratamentos. Este estudo de caso discute alternativas inovadoras de acesso para doenças raras no Brasil, com foco no acesso precoce ao alfapabinafuspe para mucopolissacaridose tipo II (MPS-II), uma doença lisossômica de armazenamento genético rara, caracterizada por uma deficiência da enzima iduronato-2-sulfatase. De setembro de 2018 a março de 2023, 20 pacientes brasileiros com MPS-II receberam alfapabinafuspe por meio de pesquisa clínica. Essa terapia de reposição enzimática (TRE) atravessa a barreira hematoencefálica para tratar manifestações do sistema nervoso central não atendidas pelos tratamentos existentes. A participação dos pacientes no estudo clínico resultou em uma economia estimada de 65 milhões de reais para o sistema público de saúde, em comparação com a TRE convencional com idursulfase alfa, além de potencialmente melhores resultados clínicos. O estudo de caso destaca a importância de mecanismos inovadores no atendimento das necessidades médicas dos pacientes. As alternativas de acesso precoce incluem: a) acesso por meio de estudos clínicos, com execução/desenvolvimento alinhada aos gestores de saúde e vinculada a estratégias futuras de acesso; b) compartilhamento de risco em nível regulatório, considerando as incertezas de eficácia e a possibilidade de retirada do mercado e reembolso em caso de resultados negativos; e c) pré-entrega do medicamento, com pagamento condicionado aos resultados positivos do estudo clínico de fase III. Embora as parcerias público-privadas em pesquisa clínica sejam subutilizadas, elas poderiam beneficiar todas as partes interessadas ao acelerar o desenvolvimento de medicamentos, facilitar o acesso precoce dos pacientes a medicamentos inovadores e gerar economias para o sistema de saúde, especialmente para doenças raras.
Subject(s)
Mucopolysaccharidosis II , Rare Diseases , Access to Essential Medicines and Health TechnologiesABSTRACT
Problema: Mudanças no perfil de morbimortalidade brasileiro têm evidenciado a importância das doenças genéticas, porém os dados epidemiológicos ainda são limitados. Desde 2014, a Política Nacional de Atenção Integral às Pessoas com Doenças Raras visa fomentar a assistência integral no Sistema Único de Saúde (SUS). Entretanto, os profissionais da atenção primária ainda não são suficientemente capacitados para a abordagem das doenças genéticas e raras. O objetivo do estudo é apresentar a experiência adquirida por um médico residente em Medicina de Família e Comunidade em um serviço de referência em doenças genéticas e raras. Método: Trata-se de um relato de experiência de estágio eletivo desenvolvido durante oito semanas no Serviço de Genética Médica do Hospital Universitário Professor Edgard Santos da Universidade Federal da Bahia (HUPES-UFBA). O estágio foi composto de rotações em ambulatórios, laboratório, enfermaria e participação em aulas teóricas. Resultados: O residente teve contato com conhecimentos e ferramentas de genética que são úteis à sua prática como médico de família e comunidade, auxiliando na atenção às pessoas com doenças genéticas e raras. Também identificou como ferramentas e princípios da atenção primária à saúde potencializam o cuidado em genética médica. Conclusão: A experiência situou o residente quanto ao seu papel na linha de cuidado em doenças raras, reforçando a responsabilidade do profissional da atenção primária na assistência integral.
Problem: Changes in the Brazilian morbidity and mortality profile have highlighted the importance of genetic diseases, but epidemiological data are still limited. Since 2014, the National Policy for Comprehensive Care of People with Rare Diseases aims to foster comprehensive care in The Brazilian Unified Health System (Sistema Único de Saúde SUS). However, primary care professionals are not yet sufficiently trained to deal with genetic and rare diseases. The objective of the study was to present the experience gained by a Family and Community Medicine resident in a reference service in genetic and rare diseases. Methods: This is an experience report of an elective internship developed during eight weeks at the Medical Genetics Service at Hospital Universitário Professor Edgard Santos of Universidade Federal da Bahia (HUPES-UFBA). The internship consisted of rotations in outpatient clinics, laboratory, infirmary, and participation in theoretical classes. Results: Residents had contact with genetics knowledge and tools that are useful to their practice as a family physician, assisting in the care of people with genetic and rare diseases. They also identified how primary health care tools and principles enhance care in Medical Genetics. Conclusion: The experience gave the residents a better understanding of their role within the line of care for rare diseases, reinforcing the primary care professionals' responsibility for comprehensive care.
Problema: Los cambios en el perfil de morbilidad y mortalidad brasileño han puesto en atención la importancia de las enfermedades genéticas, pero los datos epidemiológicos aún son limitados. Desde 2014, la Política Nacional de Atención Integral a Personas con Enfermedades Raras tiene como objetivo fomentar la atención integral en el Sistema Único de Salud (SUS). Sin embargo, los profesionales de atención primaria aún no están lo suficientemente capacitados para hacer frente a las enfermedades genéticas y raras. El objetivo del estudio es presentar la experiencia adquirida por un médico residente en Medicina Familiar y Comunitaria en un servicio de referencia en genética y enfermedades raras. Método: Se trata de un informe de experiencia de estancia electiva desarrollada durante ocho semanas en el Servicio de Genética Médica de HUPES-UFBA. La estancia consistió en rotaciones en consultas externas, laboratorio, enfermería y participación en clases teóricas. Resultados: El residente tuvo contacto con conocimientos y herramientas genéticas que le son útiles para su práctica como médico de familia y comunitario, ayudando a atender a personas con enfermedades genéticas y raras. También identificó cómo las herramientas y los principios de la atención primaria de salud mejoran la atención en Genética Médica. Conclusión: La experiencia colocó al residente en su rol dentro de la línea de atención en enfermedades raras, reforzando la responsabilidad del profesional de atención primaria en la atención integral.
Subject(s)
Health Human Resource Training , Medical Staff, Hospital/education , Primary Health Care , Rare Diseases , Professional Training , Family Practice , Genetics, MedicalABSTRACT
INTRODUCTION: Hemophagocytic syndrome results from hyperactivity of histiocytes and lymphocytes, triggered by infections, mainly viral by cytomegalovirus, Epstein-Barr and herpes. Fanconi anemia (FA) is a rare genetic disease with heterogeneous symptoms common to other diseases such as VACTERL, a disease of unknown etiology in which there are several congenital malformations. The concomitance of Fanconi and VACTERL anemia occurs in 5 to 30% of FA patients. REPORT: A 14-month-old male infant was admitted to investigate fever, hepatosplenomegaly, and granulopenia. The patient was diagnosed with hemophagocytic syndrome due to hyperferritinemia, bone marrow hemophagocytosis, transaminase elevation, decreased fibrinogen, and cytomegalovirus (CMV) infection confirmed by serology and PCR. The test with mitomycin C (MMC) showed chromosomal fragility. The patient was diagnosed with a VACTERL/FA association for having a clinic and a test compatible with both FA and VACTERL. CONCLUSION: The VACTERL/FA association is seldom described, but is present in pediatric medical practice. This study presented the main clinical-laboratory aspects and reviewed the main aspects of the concurrence of this pathology.
INTRODUÇÃO: A síndrome hemofagocítica decorre da hiperatividade de histiócitos e linfócitos e é desencadeada por infeções, principalmente virais por citomegalovírus, Epstein-barr e herpes. A anemia de Fanconi (AF) é uma doença genética rara com sintomas heterogêneos em comum a outras doenças como a associação VACTERL, uma doença de etiologia desconhecida na qual existe diversas mal formações congênitas. A concomitância da anemia de Fanconi e VACTERL é descrita em 5 a 30% dos pacientes AF. RELATO: Lactente de 14 meses, sexo masculino, admitido para investigar um quadro de febre, hepatoesplenomegalia e granulopenia. Os exames laboratoriais mostraram a hiperferritemia, elevação da transaminases, medula óssea com hemofagocitose e, sorologia e PCR positivos para citomegalovírus (CMV). O paciente foi diagnosticado com síndrome hemofagocítica por citomegalovírus. Como havia também hipoplasia do polegar esquerdo, presença de hemivértebra, agenesia renal e teste positivo de fragilidades cromossômicas com mitomicina C (MMC), o paciente foi diagnosticado com associação VACTERL/AF. CONCLUSÃO: O citomegalovírus quando infecta pacientes com problemas de imunidade como AF, apresenta risco de desencadear a síndrome hemofagocítica. A associação VACTERL/AF é pouco descrita, mas presente na prática médica da pediatria. Esse estudo descreveu os principais aspectos clínicos-laboratoriais e revisou os aspectos fundamenais descritos sobre a concomitância dessas patologias.
Subject(s)
Humans , Male , Infant , Congenital Abnormalities , Lymphohistiocytosis, Hemophagocytic , Fanconi Anemia , Chromosome Fragility , Cytomegalovirus Infections , Rare DiseasesABSTRACT
Objetivos: conhecer as estratégias de enfrentamento utilizadas pela mãe de uma lactente com Epidermólise Bolhosa. Método: estudo de caso único com abordagem qualitativa realizado com a mãe de uma criança com seis meses de idade e diagnóstico clínico de Epidermólise Bolhosa. A coleta de dados ocorreu entre fevereiro e março de 2020 no domicílio da participante, por meio de entrevista em profundidade e observação. As narrativas foram submetidas à análise de conteúdo do tipo temática. Resultados: emergiram categorias temáticas, sendo elas "O (res) significar da maternidade após o diagnóstico de Epidermólise Bolhosa", que aborda os momentos de descoberta da doença rara, bem como a utilização da internet como recurso para o enfrentamento, que apresenta o movimento para aquisição de conhecimentos teóricos para possibilitar o cuidado materno realizados à criança. Conclusão: o estudo permitiu apreender as estratégias de enfrentamento utilizadas na vivência da maternidade diante do nascimento da criança com diagnóstico de Epidermólise Bolhosa.
Objetivo: conocer las estrategias de afrontamiento utilizadas por la madre de una lactante con Epidermólisis Bullosa. Método: estudio de caso único con enfoque cualitativo realizado con la madre de una niña de seis meses de edad y diagnóstico clínico de Epidermólisis Bullosa. La recogida de datos tuvo lugar entre febrero y marzo de 2020 en el domicilio de la participante, a través de una entrevista en profundidad y observación. Las narrativas fueron sometidas al análisis de contenido del tipo temático. Resultados: surgieron categorías temáticas, siendo ellas "O (res)significar de la maternidad después del diagnóstico de Epidermólisis Ampollar", que aborda los momentos de descubrimiento de la enfermedad rara, así como la utilización de internet como recurso para el enfrentamiento, que presenta el movimiento para adquirir conocimientos teóricos para posibilitar el cuidado materno realizado a la niña. Conclusión: el estudio permitió aprehender las estrategias de enfrentamiento utilizadas en la vivencia de la maternidad ante el nacimiento del niño con diagnóstico de Epidermólisis Ampollar.
Objective: to know the coping strategies used by the mother of an infant with Epidermolysis Bullosa. Method: a single case study with a qualitative approach conducted with the mother of a six-month-old child with clinical diagnosis of Epidermolysis Bullosa. Data collection occurred between February and March 2020 at the participant's home, through in-depth interviews and observation. The narratives were submitted to thematic content analysis. Results: thematic categories emerged, being "(Re)meaning motherhood after the diagnosis of Epidermolysis Bullosa", which addresses the moments of discovery of the rare disease, as well as the use of the internet as a resource for coping, that presents the movement to acquire theoretical knowledge to enable maternal care performed to the child. Conclusion: the study allowed the understanding of the coping strategies used in the experience of motherhood before the birth of the child diagnosed with Epidermolysis Bullosa.
Subject(s)
Humans , Female , Infant , Adult , Pediatric Nursing , Epidermolysis Bullosa/prevention & control , Parenting/psychology , Rare Diseases/therapy , Qualitative ResearchABSTRACT
Introducción: Las enfermedades raras conforman las afecciones de baja prevalencia que asociadas a los medicamentos huérfanos representan un problema sanitario y social mundial. Objetivo: Revisar los aspectos más sobresalientes relacionados con las enfermedades raras, con una visión gastroenterológica, y su repercusión en la infancia. Métodos: Se realizaron búsquedas no estructuradas de publicaciones en español e inglés en PubMed, Google Scholar, Scimago, SciELO, desde enero 2010 hasta agosto 2021. Se usaron los términos: enfermedades raras, conceptualización, prevalencia, epidemiología, medicamentos huérfanos y ética. Análisis y síntesis de la información: Se revisaron las enfermedades raras en la infancia, criterios conceptuales, epidemiología global, enfermedades más reconocidas con énfasis en gastroenterología. Se destacó la prevalencia, vínculo genético, importancia social, dilema diagnóstico y categorías; repercusión de los tratamientos con medicamentos huérfanos, sus costos y problemas éticos. Se resaltó la incidencia de enfermedades digestivas y el valor de la endoscopia y la biopsia en el diagnóstico. Conclusiones: Se documentaron las enfermedades raras en la infancia, y se analizaron como problema mundial, sanitario y social. El desarrollo de la técnica y de la ciencia, resultaron contribuciones decisivas que variaron criterios sobre diferentes afecciones catalogadas como raras(AU)
Introduction: Rare diseases are the conditions of low prevalence associated with orphan drugs and they represent a global health and social problem. Objective: To review the most outstanding aspects related to rare diseases, with a gastroenterological view, and their impact on childhood. Methods: Unstructured searches for publications in Spanish and English in PubMed, Google Scholar, Scimago, SciELO were conducted, from January 2010 to August 2021. The terms rare diseases, conceptualization, prevalence, epidemiology, orphan drugs and ethics were used. Analysis and synthesis of information: Rare diseases in childhood, conceptual criteria, global epidemiology, and the most well-known diseases with emphasis on gastroenterology were reviewed. Prevalence, genetic link, social importance, diagnostic dilemma and categories, also the impact of orphan drug treatments, their costs and ethical problems were highlighted. The incidence of digestive diseases and the value of endoscopy and biopsy in diagnosis were highlighted. Conclusions: Rare diseases in childhood were documented and analyzed as a global health and social problem. The development of technique and science were decisive contributions that varied criteria on different conditions classified as rare(AU)
Subject(s)
Humans , Child, Preschool , Concept Formation , Rare Diseases/drug therapy , Rare Diseases/epidemiology , Biopsy , Digestive System Diseases/epidemiology , Endoscopy/economicsABSTRACT
Rare diseases refer to a group of single diseases with low incidence rates, complex pathogeneses, severe disease conditions, and rapid progression. Most rare diseases have a genetic background and may occur in childhood. Paying attention to the rare genetic diseases in children and performing early diagnosis and treatment can effectively delay the course of disease and improve the quality of life of children. Many rare diseases can be diagnosed with the help of various experimental techniques, but the diagnosis of rare diseases is still not widely understood. This article summarizes the laboratory diagnostic techniques currently used for rare genetic diseases in children, so as to provide clues for the diagnosis and treatment of such diseases and help to enhance the theoretical understanding and precise medical treatment of rare genetic diseases in children.
Subject(s)
Child , Humans , Rare Diseases/therapy , Quality of LifeABSTRACT
There are more than 7 000 rare diseases and approximately 475 million individuals with rare diseases globally, with children accounting for two-thirds of this population. Due to a relatively small patient population and limited financial resources allocated for drug research and development in pharmaceutical enterprises, there are still no drugs approved for the treatment of several thousands of these rare diseases. At present, there are no drugs for 95% of the patients with rare diseases, and consequently, the therapeutic drugs for rare diseases have been designated as orphan drugs. In order to guide pharmaceutical enterprises to strengthen the research and development of orphan drugs, various nations have enacted the acts for rare disease drugs, promoted and simplified the patent application process for orphan drugs, and provided scientific recommendations and guidance for the research and development of orphan drugs. Since there is a relatively high incidence rate of rare diseases in children, this article reviews the latest research on pharmacotherapy for children with rare diseases.
Subject(s)
Humans , Child , Rare Diseases/drug therapy , Orphan Drug Production , Pharmaceutical PreparationsABSTRACT
Rare diseases in children are characterized by low prevalence, complex pathogenesis, variety, and difficulty in the diagnosis and treatment. With the development of medical services, progress has been made in the diagnosis and treatment of rare diseases. However, due to asymmetric allocation of medical resources at different levels, there are still many shortcomings in the establishment and promotion of the homogenized management system of rare disease diagnosis and treatment. In order to further standardize the homogenized management of rare diseases in children, achieve early and accurate diagnosis and treatment, and improve the quality of life of the children, the Rare Disease Diagnosis and Treatment Center of Tianjin Children's Hospital (Tianjin University Children's Hospital) invited relevant experts in the field to develop recommendations for the management model of homogenized diagnosis and treatment of rare diseases in children from the aspects of information construction, hierarchical diagnosis and treatment, personnel training, scientific popularization, and multi-participation. The recommendations provide reference for the regional homogenization of clinical diagnosis and treatment management system for children with rare diseases.
Subject(s)
Humans , Child , Rare Diseases/therapy , Quality of LifeABSTRACT
A boy, aged 16 months, attended the hospital due to head and facial erythema for 15 months and vulva erythema for 10 months with aggravation for 5 days. The boy developed perioral and periocular erythema in the neonatal period and had erythema and papules with desquamation and erosion in the neck, armpit, and trigone of vulva in infancy. Blood gas analysis showed metabolic acidosis; the analysis of amino acid and acylcarnitine profiles for inherited metabolic diseases and the analysis of organic acid in urine suggested multiple carboxylase deficiency; genetic testing showed a homozygous mutation of c.1522C>T(p.R508W) in the HLCS gene. Finally the boy was diagnosed with holocarboxylase synthetase deficiency and achieved a good clinical outcome after oral biotin treatment. This article analyzes the clinical data of a child with holocarboxylase synthetase deficiency and summarizes the etiology, diagnosis, and treatment of this child, so as to provide ideas for clinicians to diagnose this rare disease.
Subject(s)
Humans , Male , Infant , Biotin/therapeutic use , Holocarboxylase Synthetase Deficiency/drug therapy , Homozygote , Mutation , Rare Diseases/drug therapyABSTRACT
El síndrome de Adams-Oliver es un trastorno congénito raro, caracterizado por aplasia cutis congénita en el cuero cabelludo, defectos terminales transversales de las extremidades y piel marmorata telangiectásica congénita. Este puede presentarse debido a diferentes patrones de herencia de tipo autosómico dominante o autosómico recesivo, o por mutaciones dominantes de novo. Aunque el síndrome de Adams-Oliver es una enfermedad poco frecuente, es importante conocer sus características clínicas y patrones de herencia, para así establecer un correcto diagnóstico y sus posibles complicaciones durante el seguimiento. En el presente estudio, se describe el caso de una adolescente con síndrome de Adams-Oliver con patrón de herencia autosómica dominante, hipertensión pulmonar y bronquitis plástica. Había varios miembros de su familia con el mismo compromiso
The Adams-Oliver syndrome is a rare congenital disorder characterized by aplasia cutis congenita of the scalp, terminal transverse limb defects, and congenital telangiectatic cutis marmorata. It can occur through different inheritance patterns: autosomal dominant, autosomal recessive, or de novo dominant mutations. Although the Adams-Oliver syndrome is a rare disease, it is essential to know its clinical characteristics and inheritance patterns, to establish a correct diagnosis and its possible complications during follow-up. In the present study, we describe the case of an adolescent with Adams-Oliver syndrome with an autosomal dominant inheritance pattern, pulmonary hypertension and plastic bronchitis, and several compromised family members.
Subject(s)
Syndrome , Rare Diseases , Ectodermal Dysplasia , Limb Deformities, Congenital , Inheritance PatternsABSTRACT
Introducción. Las enfermedades huérfanas se caracterizan por su baja prevalencia, comúnmente son de evolución crónica, debilitantes y potencialmente mortales. Objetivo. Determinar las características y los factores asociados a la mortalidad por enfermedades huérfanas en Chile, entre 2002 y 2017. Materiales y métodos. Es un estudio transversal y analítico a partir de datos secundarios oficiales del Departamento de Estadística e Información en Salud (DEIS) del Ministerio de Salud de Chile. Se calcularon las tasas de mortalidad específica, y las ajustadas por sexo y edad. Se efectuó un análisis de normalidad mediante la prueba de Kolmogórov-Smirnov. Se aplicaron la prueba de ji al cuadrado de independencia para las asociaciones y el análisis de regresión logística multivariada para determinar la probabilidad de muerte. Resultados. Durante el periodo de estudio, 10.718 defunciones se atribuyeron a enfermedades huérfanas; 53,2 % ocurrieron en mujeres. La tasa media anual de mortalidad fue de 3,9 por 100.000 habitantes: 4,1 en mujeres y 3,8 en hombres. Las principales causas de muerte, en mujeres, fueron enfermedad de Creutzfeldt-Jakob, anencefalia, hepatitis autoinmunitaria y, en hombres, enfermedad de Creutzfeldt-Jakob, distrofia muscular y anencefalia. Las mujeres tienen 1,75 más veces la posibilidad de fallecer por este grupo de enfermedades en comparación con los hombres (OR ajustado=1,75; IC95% 1,69-1,82). La mayor probabilidad de morir se presentó en los menores de 0 a 4 años (OR ajustado=15,30; IC95% 14,10-19,20). Conclusión. En Chile, las mujeres constituyeron el grupo de población de mayor riesgo de morir por enfermedades huérfanas durante los años 2002 y 2017.
Introduction: Rare diseases are characterized by their low prevalence, chronically debilitating and life-threatening nature. Objective: To determine the characteristics and factors associated with mortality due to rare diseases in Chile from 2002 to 2017. Materials and methods: We conducted an analytical cross-sectional study based on secondary mortality database from the Departamento de Estadística e Información en Salud (DEIS), Ministerio de Salud de Chile (Department of Statistics and Health Information, Chile Ministry of Health) from 2002 to 2017. The specific mortality rates adjusted by age and sex were calculated. A normality analysis was conducted using the Kolmogorov-Smirnov test. In addition, a chi-square test of independence for associations and multivariate logistic regression was applied to determine the probability of death. Results: Between 2008 and 2012 there were 10,718 deaths due to rare diseases, 53.2% of them occurred among women. The average annual mortality rate was 3.9 per 100,000 inhabitants: 4.1 in women and 3.8 in men. The main causes of mortality among women were Creutzfeldt-Jakob disease, anencephaly and autoinmune hepatitis, and among men, Creutzfeldt-Jakob disease, muscular dystrophy and anencephaly. Women are 1.75 times more likely to die than men (adjusted Odds Ratio (aOR) = 1.75; 95% CI: 1.69 - 1.82). The highest probability of dying occurred among children aged 0-4 years (aOR = 15.30; 95% CI: 14.10 - 19.20). Conclusion: Overall, the burden of mortality due to rare disease was higher among women of all ages in Chile between 2002 and 2017.
Subject(s)
Mortality Registries , Rare Diseases , Chile , Public Health , Cost of IllnessABSTRACT
Resumo A fim de analisar a produção científica acerca do acesso a medicamentos no pós-estudo por participantes de ensaios clínicos com doenças raras, realizou-se revisão integrativa da literatura nas bases Biblioteca Virtual em Saúde, Embase, PubMed, SciELO, Scopus e Web of Science, abrangendo 21 estudos. No processo analítico, surgiram duas categorias: pesquisa clínica com drogas órfãs e regulação do mercado; e acesso a drogas órfãs: história, globalização e direito à saúde. A primeira analisa questões relativas à quantidade de pacientes com doenças raras, à eficácia e à segurança dessas pesquisas e aos custos e preços dos medicamentos. A segunda trata do panorama histórico do acesso pós-estudo, da globalização dos ensaios clínicos e das dificuldades para efetivar o direito ao acesso a drogas órfãs no pós-estudo. Poucos artigos abordaram o acesso ao medicamento no pós-estudo por participantes com doenças raras como questão central, o que aponta a importância de mais estudos sobre esse tema.
Abstract This study is an integrative literature review to analyze the scientific production about post-trial drug access by participants of clinical trials for rare diseases. The search was carried out in the Virtual Health Library, Embase, PubMed, SciELO, Scopus and Web of Science databases, covering 21 studies. Two categories emerged from the analysis: clinical research with orphan drugs and market regulation; and access to orphan drugs: background, globalization and the right to health. The first analyzes issues related to the number of patients with rare diseases, the efficacy and safety of these studies and the cost and price of medications. The second addresses the historical background of post-trial access, the globalization of clinical trials and the difficulties to ensure the right to post-trial access to orphan drugs. Few articles addressed post-trial drug access by participants with rare diseases as a central issue, which points to the importance of further studies on this subject.
Resumen Se pretende analizar la producción científica sobre el acceso a medicamentos para enfermedades raras en el posestudio a partir de una revisión integradora en las bases de datos Biblioteca Virtual en Salud, Embase, PubMed, SciELO, Scopus y Web of Science, que encontraron 21 estudios. Surgieron dos categorías en el análisis: investigación clínica con medicamentos huérfanos y regulación del mercado; y acceso a medicamentos huérfanos: historia, globalización y derecho a la salud. La primera examina el número de pacientes con enfermedades raras, la eficacia y seguridad de los estudios, así como los costes y precios de los medicamentos. La segunda aborda el panorama histórico del acceso posestudio, la globalización de los ensayos clínicos y las dificultades para materializar el derecho al acceso a medicamentos huérfanos en el posestudio. Pocos estudios plantean el acceso a estos medicamentos en el posestudio, y son necesarios más estudios sobre el tema.
Subject(s)
Bioethics , Clinical Trial , Rare Diseases , Ethics, Research , Health Services AccessibilityABSTRACT
Mucopolisacaridosis de tipo III es una enfermedad rara, con una incidencia de 1 en 70 000 nacidos vivos, es la más frecuente dentro del grupo de Mucopolisacaridosis y se produce por un defecto en la vía del metabolismo del heparan sulfato. Se caracteriza por afectar a mayor profundidad el sistema nervioso central, el paciente tiene un desarrollo normal hasta aproximadamente los 1 a 3 años de edad y posteriormente empieza con deterioro progresivo, cursa con retraso del desarrollo, alteración del comportamiento y trastorno del sueño agregándose déficit motor y cuadros infecciosos, culminando en un estado de postración. La esperanza de vida oscila entre los 20 a 30 años, aunque depende del fenotipo y la principal causa de muerte fue la neumonía. El diagnóstico definitivo se consigue mediante pruebas genómicas y ensayo enzimático. No cuenta con tratamiento curativo, únicamente con paliación y soporte ante las complicaciones que va desarrollando
Mucopolysaccharidosis III is a rare disease, with an incidence of 1 in 70 000 live births, it is the most frequent within the group of Mucopolysaccharidosis and is caused by a defect in the heparan sulfate metabolism pathway. It is characterized by affecting the central nervous system in greater depth, the patient has a normal development until approximately 1 to 3 years of age and later begins with progressive deterioration, courses with developmental delay, behavioral alteration and sleep disorder, adding motor deficits and infectious pictures, culminating in a state of prostration. Life expectancy ranges from 20 to 30 years, although it depends on the phenotype, and the main cause of death is pneumonia. Definitive diagnosis is achieved by genomic tests and enzymatic assay. It does not have curative treatment, only palliation and support in the face of the complications that it develops.
Subject(s)
Rare Diseases , MetabolismABSTRACT
Introduction: Giant colonic diverticulum (GCD) is rare phenomenon, with less than 200 cases described in the literature. One of the complications of GCD is diverticulitis. To date, there is paucity of data addressing the diagnosis and management of GCD complicated by acute diverticulitis. Objective: To better understand the diagnostic tools, the initial management, and the long-term follow-up for this group of patients as well as to recommend a proper multidisciplinary approach to this infrequent disease. Method A systematic literature search was performed using the PubMed, Embase, and Cochrane databases to identify all the published studies on GCD complicated by diverticulitis. Two of the authors assessed the relevance of the included full-text papers. The articles were assessed independently. Results: In total, 12 cases were identified. Our results show that 10/11 (91%) of the patients who had computed tomography (CT) scans during the initial evaluation had a correct diagnosis. There was no case of failure to non-operative approach (7/7). The patients who had an emergency operation were treated so due to diffuse peritonitis (two patients), acute hemorrhage arising from ulcers within the diverticula (one patient), and misdiagnosis (one patient). Conclusion: Giant colonic diverticulitis is a very rare disease. Computed tomography scan is a valuable tool for the initial diagnosis as well as for treatment strategy planning. Non-operative management is a viable option for patients without diffuse peritonitis. Interval endoscopy is recommended if no contraindication exists. (AU)