Immunodeficiency 34 D81.8

IMD34 leads to a predisposition to infections by weakly virulent mycobacteria, such as Bacillus Calmette-Guerin (BCG) vaccines and non-tuberculous environmental bacteria. Affected individuals are also susceptible to the more virulent species Mycobacterium tuberculosis (Bustamante et al.2007).

Immunological, biochemical, genetic, and linkage analyses detected a thr178-to-pro (T178P; 300481.0023) mutation in the CYBB gene in these patients (Bustamante et al. 2011). In the relationship reported by Bustamante et al. (2007), Bustamante et al. (2011) identified a glu231-to-pro (Q231P; 300481.0022) mutation in the CYBB gene.

Furthermore, CYBB mutations may be associated with X-linked septic granulomatous disease (OMIM: 306400).

Bustamante et al (2007) studied a large French family in which four male maternal relatives had recurrent mycobacterial disease (recessive X-linked inheritance). Three patients had recurrent disease caused by BCG. The fourth patient suffered from recurrent tuberculosis. The infections showed tropism for lymph nodes in which granulomas with cheesy necrosis but no acid-fast bacilli were observed. The patients all responded to antibiotic therapy and/or surgical excision. A common childless maternal aunt had been successfully treated for pulmonary tuberculosis. The mother of 2 patients had a history of asymptomatic, untreated latent tuberculosis.

Bustamante et al (2011) identified a second family consisting of 3 maternally related French men, aged 36 to 41 years at the time of the report, with susceptibility to mycobacterial disease that manifested as BCG disease after neonatal vaccination.

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3. Bustamante J et al.(2007) A novel X-linked recessive form of Mendelian susceptibility to mycobacterial disease. J Med Genet 44: e65, 2007.