Clinical and Genotypic Spectrum of Chronic Granulomatous Disease in 71 Latin American Patients: First Report from the LASID Registry

• Published in: Pediatric blood & cancer Vol. 62; no. 12; pp. 2101 - 2107
• Main Authors: de Oliveira-Junior, Edgar Borges, Zurro, Nuria Bengala, Prando, Carolina, Cabral-Marques, Otavio, Pereira, Paulo Vitor Soeiro, Schimke, Lena-Friederick, Klaver, Stefanie, Buzolin, Marcia, Blancas-Galicia, Lizbeth, Santos-Argumedo, Leopoldo, Pietropaolo-Cienfuegos, Dino Roberto, Espinosa-Rosales, Francisco, King, Alejandra, Sorensen, Ricardo, Porras, Oscar, Roxo-Junior, Persio, Forte, Wilma Carvalho Neves, Orellana, Julio Cesar, Lozano, Alejandro, Galicchio, Miguel, Regairaz, Lorena, Grumach, Anete Sevciovic, Costa-Carvalho, Beatriz Tavares, Bustamante, Jacinta, Bezrodnik, Liliana, Oleastro, Matias, Danielian, Silvia, Condino-Neto, Antonio
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.12.2015; Wiley Subscription Services, Inc
• Subjects: Abscess - epidemiology; Abscess - etiology; Abscess - genetics; Adolescent; Age of Onset; bacillus Calmette-Guérin vaccine; Child; Child, Preschool; chronic granulomatous disease; Diarrhea - epidemiology; Diarrhea - etiology; Diarrhea - genetics; Female; Granulomatous Disease, Chronic - complications; Granulomatous Disease, Chronic - epidemiology; Granulomatous Disease, Chronic - genetics; Hematology; Hispanic Americans; Humans; Infant; Infant, Newborn; infections; Lymphatic Diseases - epidemiology; Lymphatic Diseases - etiology; Lymphatic Diseases - genetics; Male; Membrane Glycoproteins - genetics; Mutation; mutations; NADPH oxidase; NADPH Oxidase 2; NADPH Oxidases - genetics; Oncology; Osteomyelitis - epidemiology; Osteomyelitis - etiology; Osteomyelitis - genetics; Otitis - epidemiology; Otitis - etiology; Otitis - genetics; Pediatrics; Pneumonia - epidemiology; Pneumonia - etiology; Pneumonia - genetics; Registries; registry; Sepsis - epidemiology; Sepsis - etiology; Sepsis - genetics; Skin Diseases - epidemiology; Skin Diseases - etiology; Skin Diseases - genetics; Urinary Tract Infections - epidemiology; Urinary Tract Infections - etiology; Urinary Tract Infections - genetics; infections; registry; bacillus Calmette-Guérin vaccine; mutations; NADPH oxidase; chronic granulomatous disease
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.25674

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. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.