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01-02-2014 | Original Research

First Report of the Hyper-IgM Syndrome Registry of the Latin American Society for Immunodeficiencies: Novel Mutations, Unique Infections, and Outcomes

Authors: Otavio Cabral-Marques, Stefanie Klaver, Lena F Schimke, Évelyn H Ascendino, Taj Ali Khan, Paulo Vítor Soeiro Pereira, Angela Falcai, Alexander Vargas-Hernández, Leopoldo Santos-Argumedo, Liliana Bezrodnik, Ileana Moreira, Gisela Seminario, Daniela Di Giovanni, Andrea Gómez Raccio, Oscar Porras, Cristina Worm Weber, Janaíra Fernandes Ferreira, Fabiola Scancetti Tavares, Elisa de Carvalho, Claudia França Cavalcante Valente, Gisele Kuntze, Miguel Galicchio, Alejandra King, Nelson Augusto Rosário-Filho, Milena Baptistella Grota, Maria Marluce dos Santos Vilela, Regina Sumiko Watanabe Di Gesu, Simone Lima, Leiva de Souza Moura, Eduardo Talesnik, Eli Mansour, Pérsio Roxo-Junior, Juan Carlos Aldave, Ekaterine Goudouris, Fernanda Pinto-Mariz, Laura Berrón-Ruiz, Tamara Staines-Boone, Wilmer O. Córdova Calderón, María del Carmen Zarate-Hernández, Anete S. Grumach, Ricardo Sorensen, Anne Durandy, Troy R. Torgerson, Beatriz Tavares Costa Carvalho, Francisco Espinosa-Rosales, Hans D. Ochs, Antonio Condino-Neto

Published in: Journal of Clinical Immunology | Issue 2/2014

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.

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Title: First Report of the Hyper-IgM Syndrome Registry of the Latin American Society for Immunodeficiencies: Novel Mutations, Unique Infections, and Outcomes
Authors: Otavio Cabral-Marques
Stefanie Klaver
Lena F Schimke
Évelyn H Ascendino
Taj Ali Khan
Paulo Vítor Soeiro Pereira
Angela Falcai
Alexander Vargas-Hernández
Leopoldo Santos-Argumedo
Liliana Bezrodnik
Ileana Moreira
Gisela Seminario
Daniela Di Giovanni
Andrea Gómez Raccio
Oscar Porras
Cristina Worm Weber
Janaíra Fernandes Ferreira
Fabiola Scancetti Tavares
Elisa de Carvalho
Claudia França Cavalcante Valente
Gisele Kuntze
Miguel Galicchio
Alejandra King
Nelson Augusto Rosário-Filho
Milena Baptistella Grota
Maria Marluce dos Santos Vilela
Regina Sumiko Watanabe Di Gesu
Simone Lima
Leiva de Souza Moura
Eduardo Talesnik
Eli Mansour
Pérsio Roxo-Junior
Juan Carlos Aldave
Ekaterine Goudouris
Fernanda Pinto-Mariz
Laura Berrón-Ruiz
Tamara Staines-Boone
Wilmer O. Córdova Calderón
María del Carmen Zarate-Hernández
Anete S. Grumach
Ricardo Sorensen
Anne Durandy
Troy R. Torgerson
Beatriz Tavares Costa Carvalho
Francisco Espinosa-Rosales
Hans D. Ochs
Antonio Condino-Neto
Publication date: 01-02-2014
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 2/2014
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-013-9980-4

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