title: First report of the Hyper-IgM syndrome Registry of the Latin American Society for Immunodeficiencies: novel mutations, unique infections, and outcomes.
abstract: Hyper-IgM (HIGM) syndrome is a heterogeneous group of disorders characterized by normal or elevated serum IgM levels associated with absent or decreased IgG, IgA and IgE. Here we summarize data from the HIGM syndrome Registry of the Latin American Society for Immunodeficiencies (LASID). Of the 58 patients from 51 families reported to the registry with the clinical phenotype of HIGM syndrome, molecular defects were identified in 37 patients thus far. We retrospectively analyzed the clinical, immunological and molecular data from these 37 patients. CD40 ligand (CD40L) deficiency was found in 35 patients from 25 families and activation-induced cytidine deaminase (AID) deficiency in 2 unrelated patients. Five previously unreported mutations were identified in the CD40L gene (CD40LG). Respiratory tract infections, mainly pneumonia, were the most frequent clinical manifestation. Previously undescribed fungal and opportunistic infections were observed in CD40L-deficient patients but not in the two patients with AID deficiency. These include the first cases of pneumonia caused by Mycoplasma pneumoniae, Serratia marcescens or Aspergillus sp. and diarrhea caused by Microsporidium sp. or Isospora belli. Except for four CD40L-deficient patients who died from complications of presumptive central nervous system infections or sepsis, all patients reported in this study are alive. Four CD40L-deficient patients underwent successful bone marrow transplantation. This report characterizes the clinical and genetic spectrum of HIGM syndrome in Latin America and expands the understanding of the genotype and phenotype of this syndrome in tropical areas.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730 Lineu Prestes Avenue, São Paulo, SP, ZIP 05508-000, Brazil.
authors.forename: Otavio
authors.initials: O
authors.lastname: Cabral-Marques
authors.forename: Stefanie
authors.initials: S
authors.lastname: Klaver
authors.forename: Lena F
authors.initials: LF
authors.lastname: Schimke
authors.forename: Évelyn H
authors.initials: ÉH
authors.lastname: Ascendino
authors.forename: Taj Ali
authors.initials: TA
authors.lastname: Khan
authors.forename: Paulo Vítor Soeiro
authors.initials: PV
authors.lastname: Pereira
authors.forename: Angela
authors.initials: A
authors.lastname: Falcai
authors.forename: Alexander
authors.initials: A
authors.lastname: Vargas-Hernández
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Santos-Argumedo
authors.forename: Liliana
authors.initials: L
authors.lastname: Bezrodnik
authors.forename: Ileana
authors.initials: I
authors.lastname: Moreira
authors.forename: Gisela
authors.initials: G
authors.lastname: Seminario
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Giovanni
authors.forename: Andrea Gómez
authors.initials: AG
authors.lastname: Raccio
authors.forename: Oscar
authors.initials: O
authors.lastname: Porras
authors.forename: Cristina Worm
authors.initials: CW
authors.lastname: Weber
authors.forename: Janaíra Fernandes
authors.initials: JF
authors.lastname: Ferreira
authors.forename: Fabiola Scancetti
authors.initials: FS
authors.lastname: Tavares
authors.forename: Elisa
authors.initials: E
authors.lastname: de Carvalho
authors.forename: Claudia França Cavalcante
authors.initials: CF
authors.lastname: Valente
authors.forename: Gisele
authors.initials: G
authors.lastname: Kuntze
authors.forename: Miguel
authors.initials: M
authors.lastname: Galicchio
authors.forename: Alejandra
authors.initials: A
authors.lastname: King
authors.forename: Nelson Augusto
authors.initials: NA
authors.lastname: Rosário-Filho
authors.forename: Milena Baptistella
authors.initials: MB
authors.lastname: Grota
authors.forename: Maria Marluce
authors.initials: MM
authors.lastname: dos Santos Vilela
authors.forename: Regina Sumiko Watanabe
authors.initials: RS
authors.lastname: Di Gesu
authors.forename: Simone
authors.initials: S
authors.lastname: Lima
authors.forename: Leiva
authors.initials: L
authors.lastname: de Souza Moura
authors.forename: Eduardo
authors.initials: E
authors.lastname: Talesnik
authors.forename: Eli
authors.initials: E
authors.lastname: Mansour
authors.forename: Pérsio
authors.initials: P
authors.lastname: Roxo-Junior
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Aldave
authors.forename: Ekaterine
authors.initials: E
authors.lastname: Goudouris
authors.forename: Fernanda
authors.initials: F
authors.lastname: Pinto-Mariz
authors.forename: Laura
authors.initials: L
authors.lastname: Berrón-Ruiz
authors.forename: Tamara
authors.initials: T
authors.lastname: Staines-Boone
authors.forename: Wilmer O Córdova
authors.initials: WO
authors.lastname: Calderón
authors.forename: María
authors.initials: M
authors.lastname: del Carmen Zarate-Hernández
authors.forename: Anete S
authors.initials: AS
authors.lastname: Grumach
authors.forename: Ricardo
authors.initials: R
authors.lastname: Sorensen
authors.forename: Anne
authors.initials: A
authors.lastname: Durandy
authors.forename: Troy R
authors.initials: TR
authors.lastname: Torgerson
authors.forename: Beatriz Tavares Costa
authors.initials: BT
authors.lastname: Carvalho
authors.forename: Francisco
authors.initials: F
authors.lastname: Espinosa-Rosales
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.forename: Antonio
authors.initials: A
authors.lastname: Condino-Neto
mesh_terms: D023201:CD40 Ligand / Q000172:deficiency / Q000235:genetics; D002675:Child, Preschool; D015897:Comorbidity; D003564:Cytidine Deaminase / Q000172:deficiency / Q000235:genetics; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D007223:Infant; D007231:Infant, Newborn; D007239:Infections / Q000175:diagnosis / Q000209:etiology; D008168:Lung / Q000473:pathology; D008297:Male; D012042:Registries; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D023201:CD40 Ligand; D003564:Cytidine Deaminase