Another example of unique genetic abnormality leading to specific susceptibility to Mycobacterium avium

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Haerynck et al describe a child with fistulizing cervical lymphadenopathy and dissemination of Mycobacterium avium with subsequent severe gastrointestinal disease, malnutrition, and failure to respond to antimicrobial, surgical, nutritional therapies, and gamma interferon injections—with possible final fatal enteroviral myocarditis. Two genetic mutations in the interleukin 12–interferon gamma axis were found in the patient, and one mutation each was found heterozygously in nonconsanguineous parents.

It is not the intent of The Journal to publish each instance of discovery of a gene mutation having clinical impact. However, the luminary investigations led by the laboratories of Steven Holland in Bethesda and Jean-Laurent Casanova in Paris, elegantly elucidating myriad defects in cytokine signaling in the innate immune system that lead to unique susceptibility to certain pathogens (eg, one gene, susceptibility to one pathogen), have turned the old world of primary immunodeficiencies (one gene, susceptibility to multiple pathogens) upside down. The teachings of just 10 years ago – that disorders of B lymphotyces, T lymphocytes, phagocytes, and complement constitute the universe of primary immunodeficiency disorders – are probably the tip of the immunodeficiency iceberg. The notion that sporadic severe infections due to relatively common pathogens (eg, S. pneumoniae, herpes simplex virus) or severe infections due to relative nonpathogens (eg, nontuberculous mycobacteria) may not be “bad luck,” but may be due to specific Mendelian genetic mutations in the innate system is the “now.” Pediatricians take heed—this case report and discussion provide a focused tutorial.