Epidemiological characterization of rare diseases in Brazil: A retrospective study of the Brazilian Rare Diseases Network
Authors: de Oliveira Bibiana Mello , Bernardi Filipe Andrade , Baiochi João Francisco , Neiva Mariane Barros , Artifon Milena , Vergara Alberto Andrade , Martins Ana Maria , Grumach Anete Sevciovic , Acosta Angelina Xavier , Husny Antonette Souto El , de Freitas Rodrigues Ribeiro Bethania , Ramos Camila Ferreira , Steiner Carlos Eduardo , Kim Chong Ae , Christofolini Denise Maria , Yamada Diego Bettiol , Carvalho Ellaine Doris Fernandes , Ribeiro Erlane Marques , de Arruda Bastos Fabíola , Serpa Faradiba Sarquis , Brandão Flávia Reseda , Adjuto Giselle Maria Araujo Felix , Carvalho Isabelle , Saute Jonas Alex Morales , Junior Juan Clinton Llerena , Bueno Larissa Souza Mario , da Silva Luiz Carlos Santana , Santos Mara Lucia Schmitz Ferreira , Costa Marcela Câmara Machado , Giusti Marcia Maria Costa Giacon , Galera Marcial Francis , Filho Márcio Eloi Colombo , de Andrade Maria Denise Fernandes Carvalho , De Oliveira Cardoso Maria Teresinha , de Menezes Ferreira Marilaine Matos , Zeny Michelle , Caldato Milena Coelho Fernandes , Sorte Ney Boa , Musolino Nina Rosa de Castro , de Medeiros Paula Frassinetti Vasconcelos , Zen Paulo Ricardo Gazzola , Da Silva Raquel Tavares Boy , Maia Rayana Elias , Fock Rodrigo , Almeida Rosemarie Elizabeth Schimidt , Valle Solange Oliveira Rodrigues , Amorim Tatiana , Teixeira Thaís Bomfim , Prazeres Vania Mesquita Gadelha , de Faria Ferraz Victor Evangelista , Lima Vinicius Costa , Paiva Wagner José Martins , Schwartz Ida Vanessa Doederlein , Alves Domingos , Félix Têmis Maria ,   Raras Network Group, de Sousa Melo Adlya , da Silva Rocha Adrya Rafaela , Aragão Amanda , Braccini Amanda Delfino , Schmidt Amanda Maria , dos Santos Ana Mondadori , de Souza e Silva Ana Carolina , Lima Ana Catarina Góes Leite , Scasso Anna Luiza , Oliveira Anne Caroline Magalhães , Perico Arthur , da Silva Aniceto Bárbara , Pinheiro Barbara , Badaró Beatriz Ono , Braga Beatriz Brasil , de Oliveira Chapiesk Beatriz , Pinheiro Beatriz Felix , Pereira Beatriz , de Souza Ponce Betânia , Martins Bianca , de Eça Blenda Antunes Cacique Curçino , de Souza Bruna , Paschoalino Brunno Busnardo , Valadares Bruno , de Oliveira Caio Lôbo , Sales Camila , Alexandre Carine Pacheco , Girelli Carla Desengrini , Balluz Carolina , de Paiva Farias Carolina , Vilemar Carolina Oliveira , Arrigoni Caroline Duarte , de Almeida Passos Catharina , Harumi Catharine , Barbieri Cleber , Prado Daniel , Monteiro Daniela , da Silva Cruz Dhallya Andressa , Batista Eduardo , Naves Eduardo José Pereira , da Silva Elaine Samara Pinheiro Mendes , Teixeira Estela , Amaral Fabio , Moreira Fernanda Caroline , de Souza Flavia Liberato , Boggian Flavia , Filho Francisco André Gomes Bastos , Lôla Gabriel Lima , Pereira Gabriel , Diehl Gabrielle , Cordeiro Giovanna Pessanha , Duran Giulia , Fonseca Gustavo Foz , Mello Helena , Serpa Henrique , Veiga Henrique , Gabriel Ingrid , Formenti Isabella , de Brito Ramos Isabella , Paiva Isabella Ramos , Ferreira Janaina , Rangel Jannine Barboza , Florêncio Jôbert Pôrto , Filho Josevaldo Monteiro Maia , Dantas Júlia Emily Silva , Milke Julia Cordeiro , Rios Juliana , Pavao Julya , Angelo Kahue Aluaxe , de Oliveira Karina Montemor Klegen , de Carvalho Katheryne Barbosa , Zulszeski Kauanne , de Lima Leticia Raabe Mota , Nascimento Livia Polisseni Cotta , dos Santos Pereira Lorena Alves , Makariewicz Lorenzo , Bittencourt Luan Junio Pereira , Medeiros Luana , Vasconcelos Luana Souza , Jannuzzi Lucca Nogueira Paes , da Silva Luciana Costa Pinto , Aguilar Luisa , Chibicheski Luiza Valeria , de Oliveira Simões Luiza , Dias Maria Teresa Aires Cabral , dos Santos Mariana Lopes , Neves Mariana Pacheco Oliveira , Henriques Marina Teixeira , Leal Matheus Viganô , Tacla Milena Atique , Souza Milena Soares , da Paz Moises Ribeiro , Silva Morya , Soares Natan , da Silva Gilbert Nicole , Silva Otavio Mauricio , Sousa Paula Dourado , Rocha Paulo , Jacob Raissa Emanuelle , da Silva Raissa Vieira Leite , Carvalho Raniery Barros , Santos Raphaella Nagib Carvalho , Silva Raquel , Holanda Rebeca Pedrosa , Mourão Rebeca Falcão Lopes , de Oliveira Ricardo Cunha , Braga Rodrigo Mesquita Costa , Macely Sabrina , Morais Sergio , Mucumbi Sheila Constância Adolfo Mabote , Nhime Simei , de Sousa Stefanny Karla Ferreira , Rego Tauane Franca , Gurjão Thayane Holanda , dos Santos Gomes Thuanne Cidreira , Gazineu Tiago Ramos , Machado Victória Scheibe , Muniz Victória Feitosa , Rocha Victória , Leão Vitor , Oliveira Wendyson , Miguel Willian , de Araújo Ribeiro Yasmin , dos Santos Yasmin Amorim 
Published: October 2024

Abstract
Background
The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019.

Results
The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF.

Conclusion
This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services.