Methods: A descriptive case study. Informed consent was obtained from the family.
Results: At 2 years of age he was hospitalized for fever, cough, and weight loss. MAC was found by bronchoscopy, for which he received two years of treatment with resolution. At age 6 he presented with persistent fatigue, body aches, and nocturnal fevers. Chest CT scan showed multifocal lytic bone lesions. He was diagnosed with chronic recurrent multifocal osteomyelitis and started on ibuprofen. Due to his infection history, defects in the IL-12/ IFN-γ pathway were suspected. STAT1 phosphorylation was normal. Sequencing of STAT1 identified a novel heterozygous missense mutation at a highly conserved site, c.1378A>G, p.N460D, which is in the DNA-binding domain. Functional studies in primary patient cells and in transfected cell lines demonstrated decreased STAT1 activity, indicating a dominant loss-of-function (LOF) mutation. A whole-body MRI in follow-up demonstrated new bone lesions, biopsy of which grew MAC. The patient has been placed on appropriate antimycobacterials.
Conclusions: STAT1 LOF mutations should be considered in patients with MAC infection and multifocal lytic bone lesions.