Multifocal osteomyelitis caused by nontuberculous mycobacteria in patientswith a genetic defect of the interferon-gamma receptor

We describe three patients with multifocal osteomyelitis caused by Mycobact erium avium and a family history of one or more first degree family members diagnosed with various clinical presentations of infections with nontuberc ulous mycobacteria. There was a significant delay in the diagnosis and they had a protracted course of their illness, which responded only slowly to p rolonged multi-drug treatment. In one patient, additional treatment with in terferon-gamma (IFN-gamma) was necessary. Macrophages of these patients had decreased in vitro responsiveness to IFN-gamma. Genomic sequencing reveale d that these patients and their affected family members were heterozygous f or a previously described dominant negative mutation in the gene encoding t he IFN-gamma binding receptor-1 chain. The clinical presentations of the in fections with nontuberculous mycobacteria in these families, with spread li mited to skin, bone and lymph nodes. is discussed in the light of the immun e mechanisms that are responsible for the clearance of otherwise poorly pat hogenic environmental mycobacteria. (C) 2001 Elsevier Science B.V. All righ ts reserved.