1. Severe BCG-osis Misdiagnosed as Multidrug-Resistant Tuberculosis in an IL-12Rβ1-Deficient Peruvian Girl.
- Author
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Esteve-Sole A, Sánchez-Dávila SP, Deyà-Martínez A, Freeman AF, Zelazny AM, Dekker JP, Khil PP, Holland SM, Noguera-Julian A, Bustamante J, Casanova JL, Juan M, Cordova W, and Alsina L
- Subjects
- Antitubercular Agents pharmacology, Antitubercular Agents therapeutic use, Child, DNA Mutational Analysis, Female, Genetic Predisposition to Disease, Humans, Mutation, Mycobacterium tuberculosis drug effects, Peru, Prognosis, Severity of Illness Index, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant microbiology, BCG Vaccine immunology, Disease Susceptibility, Mycobacterium tuberculosis immunology, Receptors, Interleukin-12 deficiency, Tuberculosis, Multidrug-Resistant genetics, Tuberculosis, Multidrug-Resistant immunology
- Abstract
Purpose: Mendelian suceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency predisposing to severe disease caused by mycobacteria and other intracellular pathogens. Delay in diagnosis can have an impact on the patient's prognosis., Methods: We evaluated the IFN-γ circuit by studying IFN-γ production after mycobacterial challenge as well as IL-12Rβ1 expression and STAT4 phosphorylation in response to IL-12p70 stimulation in whole blood of a 6-year-old Peruvian girl with disseminated recurrent mycobacterial infection diagnosed as multidrug-resistant tuberculosis. Genetic studies with Sanger sequencing were used to identify the causative mutation. Microbiological studies based on PCR reactions were used to diagnose the specific mycobacterial species., Results: We identified a homozygous mutation in the IL12RB1 gene (p. Arg211*) causing abolished expression of IL-12Rβ1 and IL-12 response. MSMD diagnosis led to a microbiological reevaluation of the patient, revealing a BCG vaccine-related infection instead of tuberculosis. Treatment was then adjusted, with good response., Conclusions: We report the first Peruvian patient with IL-12Rβ1 deficiency. Specific mycobacterial species diagnosis within Mycobacterium tuberculosis complex is still challenging in countries with limited access to PCR-based microbiological diagnostic techniques. Awareness of MSMD warning signs and accurate microbiological diagnosis of mycobacterial infections are of the utmost importance for optimal diagnosis and management of affected patients.
- Published
- 2018
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