INTRODUCTION: Urea cycle disorders (UCDs) represent a group of rare diseases (RDs) characterized by impaired ammonia detoxification, leading to significant challenges in diagnosis and management. The Brazilian Rare Diseases Network (RARAS) aims to conduct an epidemiological surveillance of RD in 40 health centers from all regions of the country. OBJECTIVE: Present the epidemiological profile of UCDs cases in RARAS Network. MATERIALS AND METHODS: Data from patients with suspected and confirmed UCD diagnoses were extracted from RARAS REDCap database, from retrospective (2018-2019) and prospective (2022-2023) approaches. RESULTS: Fourteen individuals were identified with a UCD diagnosis of almost 20 thousand cases registered in the RARAS database. One case had suspected diagnosis (waiting for confirmatory tests), two were diagnosed through neonatal screening and 11 were diagnosed postnatally. The most prevalent disorders were Argininemia (n=4), Ornithine transcarbamylase deficiency (n=3), and Citrullinemia type I (n=3). Diagnoses were either biochemical (69.2%) or molecular (30.8%). Unified Health System (SUS) funded 69.2% of diagnoses. The interval until diagnosis ranged from 36 days to 27 years and 4 months (median of 3 years and 3 months). Also, 78.5% patients reported receiving treatment, of which 64.2% relied on private sources. The most consulted medical specialties were neurology or pediatric neurology (77.7%), followed by gastroenterology and hepatology (44.4%). The most common signs and symptoms, registered through the Human Phenotype Ontology, were hyperammonemia (n=5); jaundice; vomiting; seizure and intellectual disability (n=3). Nine patients (64.3%) registered hospitalizations (mean: 2.22 per patient), mainly due to UCD (ICD-10 E72.2). No death was reported in the studied period. CONCLUSION: Currently, in Brazil, the Neonatal Screening Program does not encompass tests for UCDs; nevertheless, a few states have implemented expanded neonatal screening. The two cases in this study were born in these locations. This study highlights the need to support UCD diagnosis through neonatal screening as early diagnosis is essential to therapeutic interventions and patient outcomes improvements. These results show the importance of public policies with SUS as the main funding source for diagnosis and management of UCDs patients.

INTRODUÇÃO: De acordo com a American Society of Human Genetics, aconselhamento genético (AG) é o processo de comunicação que trata dos problemas humanos relacionados com a ocorrência, ou risco de ocorrência, de uma doença genética dentro de uma família - realizado por uma equipe multidisciplinar capacitada. O AG é responsável, dentre outras funções, pela melhor compreensão do diagnóstico e da repercussão clínica desse, pelo entendimento da hereditariedade e do risco de recorrência e pelo estabelecimento de possíveis alternativas. Considerando que cerca de 80% das Doenças Raras são de origem genética, o AG é fundamental na atenção dos indivíduos acometidos e suas famílias. Segundo a Portaria 199/2014 da Política Nacional das Doenças Raras, apenas os Serviços de Referência em Doenças Raras (SRDR) ou Serviços Especializados em Doenças Raras (SEDR) estão habilitados a realizar AG. OBJETIVO: Avaliar o impacto financeiro de procedimentos ambulatoriais de AG no Sistema Único de Saúde no Brasil. MÉTODOS: Estudo descritivo retrospectivo documental a partir de dados disponibilizados pelo Departamento de Informática do Sistema Único de Saúde no período entre maio/2020 e maio/2021. RESULTADOS: No período avaliado, foram registrados 3,3 bilhões de procedimentos ambulatoriais no Brasil. Destes, 7800 foram AG (2,3:1.000.000). A média mensal foi de 600 procedimentos (±235,6), com aumento progressivo no período. A maior parte dos procedimentos foram registrados na Região Sul (45,8%), e nenhum foi registrado na Região Norte. Dentre os Estados brasileiros que realizaram AG, os mais frequentes foram: Rio Grande do Sul (43,4%), Ceará (15,7%) e Rio de Janeiro (12,5%). O investimento envolvendo AG foi de R$780 mil, cerca de 0,004% das despesas totais de procedimentos ambulatoriais no período estudado. CONCLUSÃO: A discrepância na distribuição regional de procedimentos ambulatoriais de AG reflete a desigualdade de acesso e distribuição dos serviços de atendimento especializado dentro do território nacional - haja vista que não há por ora serviços habilitados a realizar AG na Região Norte. Essa diferença é preocupante, uma vez que os pacientes e seus familiares necessitam de acesso às informações necessárias para um melhor entendimento e abordagem das doenças de causa genética.

Abstract Background: A rare disease is a medical condition with low prevalence in the general population, but these can collectively affect up to 10% of the population. Thus, rare diseases have a significant impact on the health care system, and health professionals must be familiar with their diagnosis, management, and treatment. Objective: This paper aims to provide health indicators regarding the rare diseases in Brazil and to create a network of reference centers with health professionals from different regions of the country. RARASnet proposes to map, analyze, and communicate all the data regarding the infrastructure of the centers and the patients' progress or needs. The focus of the proposed study is to provide all the technical infrastructure and analysis, following the World Health Organization and the Brazilian Ministry of Health guidelines. Methods: To build this digitized system, we will provide a security framework to assure the privacy and protection of each patient when collecting data. Systems development life cycle methodologies will also be applied to align software development, infrastructure operation, and quality assurance. After data collection of all information designed by the specialists, the computational analysis, modeling, and results will be communicated in scientific research papers and a digital health observatory. Results: The project has several activities, and it is in an initial stage. Initially, a survey was given to all health care centers to understand the technical aspects of each network member, such as the existence of computers, technical support staff, and digitized systems. In this survey, we detected that 59% (23/39) of participating health units have electronic medical records, while 41% (16/39) have paper records. Therefore, we will have different strategies to access the data from each center in the data collection phase. Later, we will standardize and analyze the clinical and epidemiological data and use these data to develop a national network for monitoring rare diseases and a digital health observatory to make the information available. The project had its financing approved in December 2019. Retrospective data collection started in October 2020, and we expect to finish in January 2021. During the third quarter of 2020, we enrolled 40 health institutions from all regions of Brazil. Conclusions: The nature of rare disease diagnosis is complex and diverse, and many problems will be faced in the evolution of the project. However, decisions based on data analysis are the best option for the improvement of the rare disease network in Brazil. The creation of RARASnet, along with all the digitized infrastructure, can improve the accessibility of information and standardization of rare diseases in the country.