The Brazilian Policy of Comprehensive Care for People with Rare Diseases (BPCCPRD) was established by the Ministry of Health to reduce morbidity and mortality and improve the quality of life of people with rare diseases (RD). Several laboratory tests, most using molecular genetic technologies, have been incorporated by the Brazilian Public Health System, and 18 specialised centres have so far been established at university hospitals (UH) in the capitals of the Southern, Southeastern and Northeastern regions. However, whether the available human and technological resources in these services are appropriate and sufcient to achieve the goals of care established by the BPCCPRD is unknown. Despite great advances in diagnosis, especially due to new technologies and the recent structuring of clinical assessment of RD in Brazil, epidemiological data are lacking and when available, restricted to specifc disorders. This position paper summarises the performance of a nationally representative survey on epidemiology, clinical status, and diagnostic and therapeutic resources employed for individuals with genetic and non-genetic RD in Brazil. The Brazilian Rare Disease Network (BRDN) is under development, comprising 40 institutions, including 18 UH, 17 Rare Diseases Reference Services and fve Newborn Screening Reference Services. A retrospective study will be initially conducted, followed by a prospective study. The data collection instrument will use a standard protocol with sociodemographic data and clinical and diagnostic aspects according to international ontology. This great collaborative network is the frst initiative of a large epidemiological data collection of RD in Latin America, and the results will increase the knowledge of RD in Brazil and help health managers to improve national public policy on RD in Brazil.

INTRODUCTION: The newborn screening (NBS) enables early diagnosis and treatment of several rare diseases (RD). Besides red reflex, hearing and pulse oximetry screening, the Brazilian NBS Program involves a blood spot test, including Phenylketonuria; Congenital hypothyroidism; Cystic fibrosis (CF); Congenital adrenal hyperplasia; Biotinidase deficiency and Sickle cell anemia. Given the limited epidemiological data on RD in Brazil, the Brazilian Rare Diseases Network (RARAS) was established aiming to perform a national survey on RD. OBJECTIVES: To analyze the epidemiological data of RD diagnosed through NBS in Brazil using data from the RARAS network. MATERIALS AND METHODS: Retrospective data of cases with confirmed or suspected RD diagnosis in the RARAS' centers between 2018-2019 were collected using RedCap. All cases diagnosed through NBS were included. RESULTS: Out of 12,530 RARAS records, 900 (7.18%) were diagnosed through NBS. Most were born in the Southeast region (42.38%), were female (66.56%) and admixed (50.59%). The mean age at data collection was 12.97 years (±10.54). Diagnosis was confirmed in 97.71% cases; 2.29% were under investigation. The Brazilian Unified Health System funded most diagnoses (98.27%). The most frequent diagnoses were Phenylketonuria (n=454); Congenital hypothyroidism (n=145) and CF (n=117). When excluding the pathologies from the public NBS Program, the most prevalent disorders were Maple syrup urine disease (n=15), Glucose-6-phosphate dehydrogenase deficiency and Galactosemia (n=5). Familial recurrence rate was 12.20% and consanguinity rate was 11.46%. Hospitalization was reported by 201 (22.89%), with a mean of 2.37 hospitalizations/participant, mainly due to CF. The mortality rate was 0.34%, with aminoacidopathies as the leading cause of death. CONCLUSIONS: The low mortality rate of this population compared to the Brazilian infant mortality rate in 2019 (1.33%), and the reduced hospitalization rate compared to the general RARAS' rate (4.12), underline the importance of early diagnosis through NBS for better outcomes. Furthermore, the higher consanguinity rate compared to the Brazilian (1.60%) and RARAS' rate (6.40%), may be due to the autosomal recessive inheritance of most screened diseases. Data show the importance of early diagnosis of life-threatening disorders that were not diagnosed in the public NBS, highlighting the necessity of expansion of screened disorders in this program.

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.