Immunodeficiency 29 D81.9

Rare immunodeficiency caused by impairment of interferon-gamma-mediated immunity. It is characterized by a predisposition to disease caused by moderately virulent mycobacterial species such as Bacillus Calmette-Guerin (BCG) vaccine, nontuberculous mycobacteria, and the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in persons susceptible to mycobacterial infections, with the exception of Salmonella, which infects less than 50% of these persons. The severity of clinical disease depends on the degree of impairment of interferon-gamma-mediated immunity. Some patients may die from mycobacterial disease in early childhood, while others develop disseminated but curable infections with tuberculous granulomas later in life.

Etiopathogenetically, a massively impaired IL12B secretion underlies this immunodeficiency syndrome. Affected individuals usually have BCG disease following childhood vaccination, and at least half also have Salmonella infection.

The disease phenotype is relatively mild, and patients have a good prognosis.

Altare et al (1998) described IL12 deficiency in a child with curable BCG and Salmonella enteritidis infection. The girl was born to consanguineous Pakistani parents and received BCG vaccination at birth. Three months later, the child presented with local ulceration at the vaccination site in the left deltoid muscle area, regional lymphadenopathy, and a draining sinus from which M. bovis BCG was isolated.

Picard et al (2002) reported 12 additional patients with IL12B deficiency from 5 other family strains and reviewed the phenotype of all patients. Of the 13 patients with IL12 deficiency, including the patient originally reported by Altare et al (1998), one child had only salmonellosis and 12 suffered from clinical disease due to BCG or environmental nontuberculous mycobacteria. One patient also had clinical disease due to virulent Mycobacterium tuberculosis, 5 patients had clinical disease due to Salmonella serotypes, and 1 patient had clinical disease due to Nocardia asteroides. The clinical course varied from case to case. Five patients aged 2 to 11 years died from overwhelming infection, whereas 8 patients aged 3 to 12 years were still in good health and not taking antibiotics at the time of the report.

1. Al-Muhsen S et al (2008) The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. J Allergy Clin Immun 122: 1043-1051.
2. Altare F et al (1998) Inherited interleukin 12 deficiency in a child with bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J Clin Invest 102: 2035-2040.
3. Picard C et al (2002) Inherited interleukin-12 deficiency: IL12B genotype and clinical phenotype of 13 patients from six kindreds. Am J Hum Genet 70: 336-348.