ABSTRACT
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12Rß1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.
Subject(s)
Mycobacterium Infections , Mycobacterium bovis , Male , Female , Humans , Retrospective Studies , BCG Vaccine , Genetic Predisposition to Disease , Mexico/epidemiology , Receptors, Interleukin-12/genetics , Mycobacterium Infections/epidemiology , Mycobacterium Infections/geneticsABSTRACT
Mutations in recombinase activating genes 1 and 2 (RAG1/2) result in human severe combined immunodeficiency (SCID). The products of these genes are essential for V(D)J rearrangement of the antigen receptors during lymphocyte development. Mutations resulting in null-recombination activity in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with hypomorphic mutations may develop leaky SCID, including Omenn syndrome (OS). A group of previously unrecognized clinical phenotypes associated with granulomata and/or autoimmunity have been described as a consequence of hypomorphic mutations. Here, we present six patients from unrelated families with missense variants in RAG1 or RAG2. Phenotypes observed in these patients ranged from OS to severe mycobacterial infections and granulomatous disease. Moreover, we report the first evidence of two variants that had not been associated with immunodeficiency. This study represents the first case series of RAG1- or RAG2-deficient patients from Mexico and Latin America.
Subject(s)
DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , Homeodomain Proteins/genetics , Mutation/genetics , Mutation/immunology , Nuclear Proteins/deficiency , Nuclear Proteins/genetics , Adolescent , Child , Female , Humans , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/immunology , Infant , Lymphocytes/immunology , Male , Mexico , PhenotypeABSTRACT
BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. OBJECTIVE: Our objective was to assess the effect of mycobacterial disease in patients with CGD. METHODS: We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. RESULTS: Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. CONCLUSION: Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.
Subject(s)
Granulomatous Disease, Chronic/complications , Mycobacterium Infections/diagnosis , Mycobacterium Infections/etiology , BCG Vaccine/administration & dosage , Bacterial Infections/diagnosis , Bacterial Infections/epidemiology , Bacterial Infections/etiology , Bacterial Infections/mortality , Child , Child, Preschool , Female , Granulomatous Disease, Chronic/epidemiology , Granulomatous Disease, Chronic/mortality , Granulomatous Disease, Chronic/therapy , Humans , Infant , Male , Mycobacterium Infections/epidemiology , Mycobacterium Infections/mortality , Mycoses/diagnosis , Mycoses/epidemiology , Mycoses/etiology , Mycoses/mortality , Patient Outcome Assessment , Retrospective Studies , Tuberculosis/diagnosis , Tuberculosis/etiologyABSTRACT
Churg-Strauss syndrome (CSS) is one of the rarest forms of vasculitis, and very rarely presents in the pediatric population. We present two cases of childhood CSS, both with hepatic and cardiac involvement. To our knowledge, these are the first two cases of CSS in the pediatric population described in Mexico.
