Disseminated BCG Infection Revealing Mendelian Susceptibility to Mycobacterial Disease in an Infant with IFNGR1 Deficiency

Introduction Mendelian susceptibility to mycobacterial disease (MSMD) is a group of immune disorders causing increased risk of mycobacterial and other intracellular infections, with mutations in the interferon-γ receptor 1 (IFN-γR1) among the first described causes. Case Report A 6-month-old girl, second child of consanguineous parents from rural Mexico, had a sibling who died at 4 months from ganglionar tuberculosis and disseminated mycobacteriosis linked to a confirmed IFNGR1 mutation. She received BCG (vaccine stands for Bacillus Calmette–Guérin) at birth. At 4 months, she developed right axillary lymphadenopathy that partially improved; at 5 months, it recurred with inflammation, respiratory symptoms, pancytopenia, and an erythematous, scaly rash. A biopsy drained pus and cultured positive for mycobacteria; she was treated with a cephalosporin, metronidazole, and anti-tuberculous therapy. Referred to tertiary care for respiratory instability, she presented mild malnutrition, microcephaly, holosystolic murmur, ascites, hepatomegaly (4 cm), splenomegaly (7 cm), severe diaper dermatitis, and an axillary mass. Disseminated BCG disease was diagnosed; treatment continued with anti-tuberculous drugs, steroids, human immunoglobulin therapy, and prophylaxis with trimethoprim/sulfamethoxazole and fluconazole. Labs showed normocytic anemia, anisocytosis, thrombocytopenia, hypoalbuminemia, direct hyperbilirubinemia, and severe hypoglycemia. Ultrasound showed hepatosplenomegaly, portal hypertension, and bilateral cervical lymphadenopathy; bone marrow was normal. Gastric bacilloscopy, HIV, and viral PCR were negative except for Acinetobacter baumannii in a respiratory panel. She developed sepsis-related cholestasis, coagulopathy, factor XII deficiency, colitis, catheter-related infection, suspected fungal infection, and ventilator-associated pneumonia due to A. baumannii, treated with broad-spectrum antibiotics. Given the family history, IFNGR1 sequencing confirmed a pathogenic homozygous nonsense mutation c.672G>A (p.Trp224*); both parents were heterozygous carriers. Discussion In countries with routine BCG vaccination, recognizing possible inborn errors of immunity and assessing family history support early diagnosis and appropriate treatment.