Interleukin-12 receptor beta 1 (IL-12R beta 1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guerin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years +/- 9.8 years (range, 0.5-46.4 yr). IL-12R beta 1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.
C1 [de Beaucoudrey, Ludovic; Samarina, Arina; Bustamante, Jacinta; Cobat, Aurelie; Boisson-Dupuis, Stephanie; Feinberg, Jacqueline; Janniere, Lucile; Rose, Yoann; de Suremain, Maylis; Kong, Xiao-Fei; Filipe-Santos, Orchidee; Chapgier, Ariane; Picard, Capucine; Abel, Laurent; Casanova, Jean-Laurent] INSERM, U980, Lab Human Genet Infect Dis, Paris, France.
[Fischer, Alain] INSERM, U768, Lab Normal & Pathol Dev Immune Syst, Paris, France.
[de Beaucoudrey, Ludovic; Samarina, Arina; Bustamante, Jacinta; Cobat, Aurelie; Boisson-Dupuis, Stephanie; Feinberg, Jacqueline; Janniere, Lucile; Rose, Yoann; de Suremain, Maylis; Kong, Xiao-Fei; Filipe-Santos, Orchidee; Chapgier, Ariane; Picard, Capucine; Fischer, Alain; Abel, Laurent; Casanova, Jean-Laurent] Univ Paris 05, Necker Med Sch, Paris, France.
[Samarina, Arina; Boisson-Dupuis, Stephanie; Kong, Xiao-Fei; Abel, Laurent; Casanova, Jean-Laurent] Rockefeller Univ, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.
[Al-Muhsen, Saleh; Al-Hajjar, Sami; Alangari, Abdullah; Casanova, Jean-Laurent] King Saud Univ, Coll Med, Prince Naif Ctr Immunol Res, Riyadh 11461, Saudi Arabia.
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[Picard, Capucine] Hop Necker Enfants Malad, AP HP, Study Ctr Primary Immunodeficiencies, Paris, France.
[Fischer, Alain; Casanova, Jean-Laurent] Hop Necker Enfants Malad, AP HP, Pediat Hematol Immunol Unit, Paris, France.
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[Tanir, Gonul] Sami Ulus Children Hlth & Dis Training & Res Ctr, Ankara, Turkey.
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[Matsuoka, Masao] Kyoto Univ, Inst Virus Res, Lab Virus Control, Kyoto 606, Japan.
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[Siegrist, Claire-Anne] Univ Geneva, Dept Pediat, Geneva, Switzerland.
[Frecerova, Klara] Minist Hlth, Dept Int Relat, Bratislava, Slovakia.
[Blueetters-Sawatzki, Renate] Dept Pediat Hematol & Oncol, Giessen, Germany.
[Bernhoeft, Jutta] Hannover Med Sch, Dept Pediat Pulmonol & Neonatol, D-3000 Hannover, Germany.
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[Lammas, David] Univ Birmingham, Sch Med, MRC, Ctr Immune Regulat, Birmingham, W Midlands, England.
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Catholic Univ Louvain, B-1200 Brussels, Belgium.
[Tuerlinckx, David] Catholic Univ Louvain, Dept Pediat, Mt Godinne Clin, B-1200 Brussels, Belgium.
[Nieuwhof, Chris] Maastricht Univ, Med Ctr, Dept Internal Med, Div Clin & Expt Immunol, Maastricht, Netherlands.
[Haas, Walther H.] Robert Koch Inst, Dept Infect Dis Epidemiol, Unit Resp Infect, D-1000 Berlin, Germany.
[Mueller-Fleckenstein, Ingrid; Fleckenstein, Bernhard] Univ Erlangen Nurnberg, Inst Klin & Mol Virol, D-8520 Erlangen, Germany.
[Levy, Jacob] Ben Gurion Univ Negev, Fac Hlth Sci, Soroka Med Ctr, Dept Pediat, Beer Sheva, Israel.
[Raj, Revathi] Apollo Special Hosp, Dept Pediat Hematol, Madras, Tamil Nadu, India.
[Cohen, Aileen Cleary; Lewis, David B.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
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Chang Gung Childrens Hosp, Dept Med Res, Kaohsiung, Taiwan.
Chang Gung Univ, Kaohsiung, Taiwan.
[Wang, Xiaochuan] Fudan Univ, Dept Clin Immunol, Childrens Hosp, Shanghai 200433, Peoples R China.
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[Castro, Gabriela] Univ Fed Bahia, Dept Immunol, BR-41170290 Salvador, BA, Brazil.
[Natera, Ivelisse] Univ Hosp Caracas, Caracas, Venezuela.
[Codoceo, Ana; King, Alejandra] Hosp Ninos Luis Calvo Mackenna, Santiago, Chile.
[Bezrodnik, Liliana; Di Giovani, Daniela; Isabel Gaillard, Maria] Ricardo Gutierrez Children Hosp, Dept Immunol, Buenos Aires, DF, Argentina.
[de Moraes-Vasconcelos, Dewton; Grumach, Anete Sevciovic; da Silva Duarte, Alberto Jose] Univ Sao Paulo, Sch Med, Dept Dermatol, Lab Invest Dermatol & Immunodeficiencies, Sao Paulo, Brazil.
[Aldana, Ruth] Childrens Hosp Federico Gomez, Dept Pulmonol, Mexico City, DF, Mexico.
[Javier Espinosa-Rosales, Francisco] Natl Inst Pediat, Dept Immunol, Mexico City, DF, Mexico.
[Bejaoui, Mohammed] Natl Ctr Bone Marrow Graft, Tunis, Tunisia.
[Bousfiha, Ahmed Aziz] Ibn Rochd Hosp, Clin Immunol Unit, Casablanca, Morocco.
[El Baghdadi, Jamila] Mil Hosp Mohamed V, Immunol Lab, Hay Riad Rabat, Morocco.
[Ozbek, Namik] Baskent Univ, Sch Med, Dept Pediat, TR-06490 Ankara, Turkey.
[Keser, Melike; Somer, Ayper] Istanbul Univ, Fac Med, Dept Pediat Infect Dis & Clin Immunol, Istanbul, Turkey.
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