ABSTRACT
Latin American geneticists have been contributing to the scientific development of Human and Medical Genetics fields since the early 1950s. In the last decades, as Medical Genetics is moving toward a new era of innovative therapies for previously untreatable conditions, the participation of Latin America in clinical trials is also increasing. This review discusses the particularities regarding funding, regulatory, and ethical aspects of conducting clinical trials for genetic diseases in Latin America, with an especial focus on Brazil, the largest country with the highest number of studies. Although there are still several barriers to overcome, the recent development of orphan drug legislation and policies for rare diseases in many Latin American countries indicates a growing opportunity for the participation of the region in international efforts for the development of new therapies for genetic diseases.
Subject(s)
Genetic Diseases, Inborn , Clinical Trials as Topic , Humans , Latin AmericaABSTRACT
Rare diseases are defined as conditions with a prevalence of no more than 6.5 per 10,000 people. Although each rare disease individually affects a small number of people, collectively, the 6,000 to 8,000 rare conditions (80% of them with genetic cause) affect around 8% of the world's population. Research about the natural history and underlying pathophysiological mechanisms of rare diseases, as well as clinical trials with new drugs, are important and necessary to develop new strategies for the treatment of these conditions. This report describes the experience of a clinical research group working with rare diseases in a reference center for lysosomal diseases in Brazil (Medical Genetics Service, Hospital de Clínicas de Porto Alegre). The activities of this research group enabled its participation in several international multicenter clinical research protocols related to the natural history or therapy development for rare genetic diseases. This participation has allowed the development of personal skills and institutional facilities for clinical research. The clinical research developed in our center has raised the quality of the medical assistance provided to non-clinical research patients in addition to enabling early access to new therapies to many patients with orphan conditions.
ABSTRACT
OBJECTIVE: To characterize the fracture pattern and the clinical history at the time of diagnosis of osteogenesis imperfecta. METHODS: In this retrospective study, all patients with osteogenesis imperfecta, of both genders, aged 0-18 years, who were treated between 2002 and 2014 were included. Medical records were assessed to collect clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, positive familial history of osteogenesis imperfecta, and the site of the fractures. In addition, radiographic findings at the time of the diagnosis were reviewed. RESULTS: Seventy-six patients (42 females) were included in the study. Individuals' age ranged from 0 to 114 months, with a median (interquartile range) age of 38 (6-96) months. Blue sclerae were present in 93.4% of patients, dentinogenesis imperfecta was observed in 27.6% of patients, and wormian bones in 29.4% of them. The number of fractures at diagnosis ranged from 0 to 17, with a median of 3 (2-8) fractures. Forty (57%) patients had fractures of the upper and lower extremities, and 9 patients also had spinal fractures. The diagnosis was performed at birth in 85.7% of patients with type 3, and 39.3% of those with type 4/5 of the disorder. CONCLUSIONS: Osteogenesis imperfecta is a genetic disorder with distinctive clinical features such as bone fragility, recurrent fractures, blue sclerae, and dentinogenesis imperfecta. It is important to know how to identify these characteristics in order to facilitate the diagnosis, optimize the treatment, and differentiate osteogenesis imperfecta from other disorders that also can lead to fractures.
OBJETIVO: Caracterizar o padrão de fraturas e a história clínica no momento do diagnóstico de osteogênese imperfeita. MÉTODOS: Neste estudo retrospectivo, foram incluídos todos os pacientes com osteogênese imperfeita de ambos os sexos, com idades entre 0 e 18 anos, que realizaram tratamento entre 2002 e 2014. Os prontuários médicos foram revisados para coleta de dados clínicos, incluindo presença de escleras azuladas, dentinogênese imperfeita, história familiar positiva para a doença e locais das fraturas, além de achados radiográficos no momento do diagnóstico. RESULTADOS: Foram incluídos no estudo 76 pacientes (42 do sexo feminino), com idade, no momento do diagnóstico, entre 0 e 114 meses [mediana (p25-p75) de idade de 38 (6-96) meses]. Escleras azuladas estavam presentes em 93,4% dos pacientes, dentinogênese imperfeita foi observada em 27,6% e ossos wormianos em 29,4%. O número de fraturas ao diagnóstico variou entre 0 e 17, com uma mediana de 3 (2-8) fraturas. Em 40 (57%) pacientes, as fraturas eram de membros superiores e inferiores no momento do diagnóstico e, em 9 pacientes também havia fratura vertebral. O diagnóstico foi realizado ao nascimento em 85,7% dos pacientes com o tipo 3 e em 39,3% daqueles com tipo 4/5 da doença. CONCLUSÕES: Osteogênese imperfeita é uma doença genética com características clínicas distintas, tais como fragilidade óssea, fraturas recorrentes, escleras azuladas e dentinogênese imperfeita. É importante saber identificar essas características, facilitando o diagnóstico, otimizando o tratamento e diferenciando de outras doenças que também podem causar fraturas.
Subject(s)
Fractures, Spontaneous/etiology , Osteogenesis Imperfecta/complications , Osteogenesis Imperfecta/diagnosis , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective StudiesABSTRACT
RESUMO Objetivo: Caracterizar o padrão de fraturas e a história clínica no momento do diagnóstico de osteogênese imperfeita. Métodos: Neste estudo retrospectivo, foram incluídos todos os pacientes com osteogênese imperfeita de ambos os sexos, com idades entre 0 e 18 anos, que realizaram tratamento entre 2002 e 2014. Os prontuários médicos foram revisados para coleta de dados clínicos, incluindo presença de escleras azuladas, dentinogênese imperfeita, história familiar positiva para a doença e locais das fraturas, além de achados radiográficos no momento do diagnóstico. Resultados: Foram incluídos no estudo 76 pacientes (42 do sexo feminino), com idade, no momento do diagnóstico, entre 0 e 114 meses [mediana (p25-p75) de idade de 38 (6-96) meses]. Escleras azuladas estavam presentes em 93,4% dos pacientes, dentinogênese imperfeita foi observada em 27,6% e ossos wormianos em 29,4%. O número de fraturas ao diagnóstico variou entre 0 e 17, com uma mediana de 3 (2-8) fraturas. Em 40 (57%) pacientes, as fraturas eram de membros superiores e inferiores no momento do diagnóstico e, em 9 pacientes também havia fratura vertebral. O diagnóstico foi realizado ao nascimento em 85,7% dos pacientes com o tipo 3 e em 39,3% daqueles com tipo 4/5 da doença. Conclusões: Osteogênese imperfeita é uma doença genética com características clínicas distintas, tais como fragilidade óssea, fraturas recorrentes, escleras azuladas e dentinogênese imperfeita. É importante saber identificar essas características, facilitando o diagnóstico, otimizando o tratamento e diferenciando de outras doenças que também podem causar fraturas.
ABSTRACT Objective: To characterize the fracture pattern and the clinical history at the time of diagnosis of osteogenesis imperfecta. Methods: In this retrospective study, all patients with osteogenesis imperfecta, of both genders, aged 0-18 years, who were treated between 2002 and 2014 were included. Medical records were assessed to collect clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, positive familial history of osteogenesis imperfecta, and the site of the fractures. In addition, radiographic findings at the time of the diagnosis were reviewed. Results: Seventy-six patients (42 females) were included in the study. Individuals' age ranged from 0 to 114 months, with a median (interquartile range) age of 38 (6-96) months. Blue sclerae were present in 93.4% of patients, dentinogenesis imperfecta was observed in 27.6% of patients, and wormian bones in 29.4% of them. The number of fractures at diagnosis ranged from 0 to 17, with a median of 3 (2-8) fractures. Forty (57%) patients had fractures of the upper and lower extremities, and 9 patients also had spinal fractures. The diagnosis was performed at birth in 85.7% of patients with type 3, and 39.3% of those with type 4/5 of the disorder. Conclusions: Osteogenesis imperfecta is a genetic disorder with distinctive clinical features such as bone fragility, recurrent fractures, blue sclerae, and dentinogenesis imperfecta. It is important to know how to identify these characteristics in order to facilitate the diagnosis, optimize the treatment, and differentiate osteogenesis imperfecta from other disorders that also can lead to fractures.
