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.

Clinical Features and Genetic Analysis of 20 Chinese Patients with X-Linked Hyper-IgM Syndrome

“…A CD40L mutation database (http://structure.bmc.lu.se/idbase/CD40Lbase/index.php) has been founded and updated [15]. Retrospective research results of XHIGM patients in Europe [16], USA [17], Japan [18], and Latin America [19] were published. However, little information about Chinese XHIGM patients has been reported.…”

Autosomal recessive hyper IgM syndrome associated with activation-induced cytidine deaminase gene in three Turkish siblings presented with tuberculosis lymphadenitis — Case report

“…Almost 40% of opportunistic infections results from PcP in the patients with HIGM syndrome [13]. Tbc has been reported as 9-28% in the patients with X linked HIGM syndrome [14][15]. In contrast to the patients with X linked HIGM syndrome, the patients with AR HIGM syndrome caused by mutations in AID gene do not have opportunistic infections.…”

Disseminated Cutaneous Warts in X-Linked Hyper IgM Syndrome

“…Clinically, patients present with sinopulmonary infections, but neutropenia, autoimmunity, liver or gastrointestinal inflammatory diseases also occur. Infections due to bacteria ( Streptococcus pneumoniae , Pseudomonas aeruginosa ) and fungi ( Pneumocystis jiroveci and candida species), and liver disease due to Cryptosporidium are common [4, 5], but susceptibility to viral infections such as papilloma virus, is not a hallmark of CD40L deficiency.…”

“…Viral infections (e.g., parvovirus B19, n = 13; herpes spp., n = 7; cytomegalovirus, n = 5) were noted in 46 cases in the USIDNET registry [4]; in the LASID registry, cytomegalovirus, hepatitis B virus, herpes simplex, molluscum contagiosum, HPV, and parainfluenza were found in one subject each [5]. To our knowledge, there is one report of a 28-year-old male with HIGM syndrome who had recurrent herpes labialis and recalcitrant warts on the hands, elbows, and knees [7].…”