Edgar Borges de Oliveira-Junior1, Nuria Bengala Zurro1, Carolina Prando2, Otavio Cabral-Marques1, Paulo Vitor Soeiro Pereira1, Lena-Friederick Schimke1, Stefanie Klaver1, Marcia Buzolin3, Lizbeth Blancas-Galicia4, Leopoldo Santos-Argumedo5, Dino Roberto Pietropaolo-Cienfuegos6, Francisco Espinosa-Rosales4, Alejandra King7, Ricardo Sorensen8, Oscar Porras9, Persio Roxo-Junior10, Wilma Carvalho Neves Forte11, Julio Cesar Orellana12, Alejandro Lozano13, Miguel Galicchio14, Lorena Regairaz15, Anete Sevciovic Grumach16, Beatriz Tavares Costa-Carvalho17, Jacinta Bustamante18,19, Liliana Bezrodnik20, Matias Oleastro21, Silvia Danielian21, Antonio Condino-Neto1. 1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. 2. Children's Hospital Little Prince, Research Institute Pelé Little Prince, Curitiba, Brazil. 3. Center for Investigation in Pediatrics, State University of Campinas Medical School, Campinas, Brazil. 4. Immunodeficiency Research Unit, National Institute of Pediatrics, Mexico City, Mexico. 5. Centro de Investigacion de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico. 6. Departamento de Alergia e Inmunología, Hospital Infantil de México "Federico Gómez", Ciudad de México, Mexico. 7. Hospital Luis Calvo Mackenna, Santiago, Chile. 8. Department of Pediatrics and JMF Diagnostic Center for PIDD, Louisiana State University Health Sciences Center, New Orleans, Louisiana. 9. Hospital Nacional de Niños, "Dr. Carlos Sáenz Herrera", San Jose, Costa Rica. 10. Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. 11. Departamento de Pediatria, Hospital Santa Casa de Misericórdia, São Paulo, Brazil. 12. Division Alergia e Inmunologia Clinica, Hospital de Ninos de la Santisima Trinidad, Cordoba, Argentina. 13. Department of Allergy and Immunology, Queen Fabiola University Clinic, Catholic University of Cordoba, Cordoba, Argentina. 14. Hospital de Niños Vitor. J. Vilela, Rosario, Argentina. 15. Unidad de Inmunología, Hospital de Niños Sor María Ludovica La Plata, Buenos Aires, Argentina. 16. Department of Medicine, ABC Medical School, Santo André, Brazil. 17. Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil. 18. Laboratory of Human Genetics of Infectious Diseases, Institut National de la Santé et de la Recherche Médicale, INSERM U1163 Imagine Institute, University Paris Descartes, Paris, France. 19. Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker-Enfants Malades Hospital, Paris, France. 20. Dr. Ricardo Gutierrez Children's Hospital, Immunology, Buenos Aires, Argentina. 21. Servicio de Inmunología y Reumatología, Hospital Nacional de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
Abstract
AIM: We analyzed data from 71 patients with chronic granulomatous disease (CGD) with a confirmed genetic diagnosis, registered in the online Latin American Society of Primary Immunodeficiencies (LASID) database. RESULTS: Latin American CGD patients presented with recurrent and severe infections caused by several organisms. The mean age at disease onset was 23.9 months, and the mean age at CGD diagnosis was 52.7 months. Recurrent pneumonia was the most frequent clinical condition (76.8%), followed by lymphadenopathy (59.4%), granulomata (49.3%), skin infections (42%), chronic diarrhea (41.9%), otitis (29%), sepsis (23.2%), abscesses (21.7%), recurrent urinary tract infection (20.3%), and osteomyelitis (15.9%). Adverse reactions to bacillus Calmette-Guérin (BCG) vaccination were identified in 30% of the studied Latin American CGD cases. The genetic diagnoses of the 71 patients revealed 53 patients from 47 families with heterogeneous mutations in the CYBB gene (five novel mutations: p.W361G, p.C282X, p.W483R, p.R226X, and p.Q93X), 16 patients with the common deletion c.75_76 del.GT in exon 2 of NCF1 gene, and two patients with mutations in the CYBA gene. CONCLUSION: The majority of Latin American CGD patients carry a hemizygous mutation in the CYBB gene. They also presented a wide range of clinical manifestations most frequently bacterial and fungal infections of the respiratory tract, skin, and lymph nodes. Thirty percent of the Latin American CGD patients presented adverse reactions to BCG, indicating that this vaccine should be avoided in these patients.
AIM: We analyzed data from 71 patients with chronic granulomatous disease (CGD) with a confirmed genetic diagnosis, registered in the online Latin American Society of Primary Immunodeficiencies (LASID) database. RESULTS: Latin American CGDpatients presented with recurrent and severe infections caused by several organisms. The mean age at disease onset was 23.9 months, and the mean age at CGD diagnosis was 52.7 months. Recurrent pneumonia was the most frequent clinical condition (76.8%), followed by lymphadenopathy (59.4%), granulomata (49.3%), skin infections (42%), chronic diarrhea (41.9%), otitis (29%), sepsis (23.2%), abscesses (21.7%), recurrent urinary tract infection (20.3%), and osteomyelitis (15.9%). Adverse reactions to bacillus Calmette-Guérin (BCG) vaccination were identified in 30% of the studied Latin American CGD cases. The genetic diagnoses of the 71 patients revealed 53 patients from 47 families with heterogeneous mutations in the CYBB gene (five novel mutations: p.W361G, p.C282X, p.W483R, p.R226X, and p.Q93X), 16 patients with the common deletion c.75_76 del.GT in exon 2 of NCF1 gene, and two patients with mutations in the CYBA gene. CONCLUSION: The majority of Latin American CGDpatients carry a hemizygous mutation in the CYBB gene. They also presented a wide range of clinical manifestations most frequently bacterial and fungal infections of the respiratory tract, skin, and lymph nodes. Thirty percent of the Latin American CGDpatients presented adverse reactions to BCG, indicating that this vaccine should be avoided in these patients.
Authors: Juliana Folloni Fernandes; Samantha Nichele; Liane E Daudt; Rita B Tavares; Adriana Seber; Fábio R Kerbauy; Adriana Koliski; Gisele Loth; Ana K Vieira; Luiz G Darrigo-Junior; Vanderson Rocha; Alessandra A Gomes; Vergílio Colturato; Luiz F Mantovani; Andreza F Ribeiro; Lisandro L Ribeiro; Cilmara Kuwahara; Ana L M Rodrigues; Victor G Zecchin; Beatriz T Costa-Carvalho; Magda Carneiro-Sampaio; Antonio Condino-Neto; Anders Fasth; Andrew Gennery; Ricardo Pasquini; Nelson Hamerschlak; Carmem Bonfim Journal: J Clin Immunol Date: 2018-11-24 Impact factor: 8.317
Authors: Noor Ul Akbar; Shahid Niaz Khan; Muhammad Usman Amin; Muhammad Ishfaq; Otavio Cabral-Marques; Lena F Schimke; Asif Iqbal; Ikram Ullah; Mubashir Hussain; Ijaz Ali; Nasar Khan; Nadia El Khawanky; Hazir Rahman; Taj Ali Khan Journal: Immunol Res Date: 2019-10 Impact factor: 2.829