title: Clinical and Genotypic Spectrum of Chronic Granulomatous Disease in 71 Latin American Patients: First Report from the LASID Registry.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Edgar Borges
authors.initials: EB
authors.lastname: de Oliveira-Junior
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Nuria Bengala
authors.initials: NB
authors.lastname: Zurro
authors.affiliation: Children's Hospital Little Prince, Research Institute Pelé Little Prince, Curitiba, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Prando
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Otavio
authors.initials: O
authors.lastname: Cabral-Marques
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Paulo Vitor Soeiro
authors.initials: PV
authors.lastname: Pereira
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Lena-Friederick
authors.initials: LF
authors.lastname: Schimke
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Klaver
authors.affiliation: Center for Investigation in Pediatrics, State University of Campinas Medical School, Campinas, Brazil.
authors.forename: Marcia
authors.initials: M
authors.lastname: Buzolin
authors.affiliation: Immunodeficiency Research Unit, National Institute of Pediatrics, Mexico City, Mexico.
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Blancas-Galicia
authors.affiliation: Centro de Investigacion de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Santos-Argumedo
authors.affiliation: Departamento de Alergia e Inmunología, Hospital Infantil de México "Federico Gómez", Ciudad de México, Mexico.
authors.forename: Dino Roberto
authors.initials: DR
authors.lastname: Pietropaolo-Cienfuegos
authors.affiliation: Immunodeficiency Research Unit, National Institute of Pediatrics, Mexico City, Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Espinosa-Rosales
authors.affiliation: Hospital Luis Calvo Mackenna, Santiago, Chile.
authors.forename: Alejandra
authors.initials: A
authors.lastname: King
authors.affiliation: Department of Pediatrics and JMF Diagnostic Center for PIDD, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Sorensen
authors.affiliation: Hospital Nacional de Niños, "Dr. Carlos Sáenz Herrera", San Jose, Costa Rica.
authors.forename: Oscar
authors.initials: O
authors.lastname: Porras
authors.affiliation: Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Persio
authors.initials: P
authors.lastname: Roxo-Junior
authors.affiliation: Departamento de Pediatria, Hospital Santa Casa de Misericórdia, São Paulo, Brazil.
authors.forename: Wilma Carvalho Neves
authors.initials: WC
authors.lastname: Forte
authors.affiliation: Division Alergia e Inmunologia Clinica, Hospital de Ninos de la Santisima Trinidad, Cordoba, Argentina.
authors.forename: Julio Cesar
authors.initials: JC
authors.lastname: Orellana
authors.affiliation: Department of Allergy and Immunology, Queen Fabiola University Clinic, Catholic University of Cordoba, Cordoba, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lozano
authors.affiliation: Hospital de Niños Vitor. J. Vilela, Rosario, Argentina.
authors.forename: Miguel
authors.initials: M
authors.lastname: Galicchio
authors.affiliation: Unidad de Inmunología, Hospital de Niños Sor María Ludovica La Plata, Buenos Aires, Argentina.
authors.forename: Lorena
authors.initials: L
authors.lastname: Regairaz
authors.affiliation: Department of Medicine, ABC Medical School, Santo André, Brazil.
authors.forename: Anete Sevciovic
authors.initials: AS
authors.lastname: Grumach
authors.affiliation: Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Beatriz Tavares
authors.initials: BT
authors.lastname: Costa-Carvalho
authors.affiliation: 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.|Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.affiliation: Dr. Ricardo Gutierrez Children's Hospital, Immunology, Buenos Aires, Argentina.
authors.forename: Liliana
authors.initials: L
authors.lastname: Bezrodnik
authors.affiliation: Servicio de Inmunología y Reumatología, Hospital Nacional de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors.forename: Matias
authors.initials: M
authors.lastname: Oleastro
authors.affiliation: Servicio de Inmunología y Reumatología, Hospital Nacional de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Danielian
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Condino-Neto
mesh_terms: D000038:Abscess / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D006630:Hispanic or Latino; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008206:Lymphatic Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D010019:Osteomyelitis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D010031:Otitis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D011014:Pneumonia / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D012042:Registries; D018805:Sepsis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D012871:Skin Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D014552:Urinary Tract Infections / Q000453:epidemiology / Q000209:etiology / Q000235:genetics
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human
keywords: NADPH oxidase; bacillus Calmette-Guérin vaccine; chronic granulomatous disease; infections; mutations; registry