Unmasking GATA2 Deficiency in an Adult with a Nocardia Brain Abscess

We present the case of a 50-year-old man with a history of rheumatoid arthritis, chronic bronchitis, with a history of multiple lung infections, including Mycobacterium avium complex and Aspergillus terreus starting in his late 40s. He was hospitalized for seizures secondary to enlarging known cnetral nervous system (CNS) lesions with previously negative viral PCRs, bacterial, fungal, and Acid-Fast Bacillus (AFB) cultures from brain biopsy. He underwent craniotomy for resection of a right cerebral brain abscess, which grew Nocardia abscessus. Despite surgery and broad antimicrobial treatment, after initial improvement, the patient presented in status epilepticus and was found to have acute infarcts in bilateral basal ganglia and new pulmonary infiltrates. He passed shortly after secondary to hemodynamic collapse from septic shock. Immunological workup revealed elevated IgG (2,572 mg/dL), reduced CD3 (460 cells/mm3) and CD4 cells (257 cells/mm3), and undetectable B and natural killer (NK) cells. He had adequate vaccine response to diphtheria and tetanus, but low Streptococcus pneumoniae IgG levels. His in vitro proliferation to tetanus and Candida antigens were negative. His dihydrorhodamine (DHR) was normal. Genetic testing via a primary immune deficiency panel revealed a pathogenic variant in GATA2, which is associated with autosomal-dominant GATA2 deficiency. This missense variant, c. 1192C>T (p.Arg 398Trp) has been previously reported in two patients. The gene panel testing also indirectly revealed trisomy 8 in our patient (which is one of the most common duplications in GATA2 patients with myelodysplastic syndrome), as the report showed 3 copy numbers for 5 genes along the short and long arm of chromosome 8. This case highlights the variability in presentation of GATA2 deficiency, as this is the first reported case of Nocardia brain abscess in GATA2 deficiency. It also emphasizes the importance of evaluating adults for immunodeficiency as soon as they develop recurrent, severe, or opportunistic infections. At the time of assessment, our patient was not a candidate for bone marrow transplantation due to his poor clinical status and low diffusion capacity on pulmonary function testing. This outcome may have been different if he had been diagnosed earlier in the course of recurrent lung infections.