Background: GATA2 deficiency is a genetic disorder of hematopoiesis, lymphatics and immunity, caused by autosomal dominant or sporadic mutations in GATA2. The disease has a broad phenotype encompassing immunodeficiency, myelodysplasia, leukemia, and vascular/lymphatic dysfunction as well as prominent pulmonary manifestations.

Research question: What are the pulmonary manifestations of GATA2 deficiency?

Study design and methods: A retrospective review was conducted of clinical medical records, diagnostic imaging, pulmonary pathology specimens and tests of pulmonary function RESULTS: Of 124 cases (95 probands and 29 ascertained), the lung was affected in 56%. In addition to chronic infections, pulmonary alveolar proteinosis (11 probands) and pulmonary arterial hypertension (9 probands) were present. Thoracic computed tomography found small nodules in 54% (54 probands, 12 relatives), reticular infiltrates in 40% (45 probands,4 relatives), paraseptal emphysema in 25% (30 probands, 1 relative), ground-glass opacities in 35% (41 probands, 2 relatives), consolidation in 21% (23 probands, 2 relatives) and a typical "crazy paving" pattern in 7% (8 probands, no relatives). Nontuberculous mycobacteria were the most frequent organisms associated with chronic infection. Allogeneic hematopoietic stem cell transplant successfully reversed the myelodysplasia and immune deficiency and also improved the pulmonary hypertension and pulmonary alveolar proteinosis in most cases.

Interpretation: GATA2 deficiency has prominent pulmonary manifestations. These clinical observations confirm the essential role of hematopoietic cells in many aspects of pulmonary function, including infections, alveolar proteinosis, and pulmonary hypertension, many of which precede the formal diagnosis, and many of which respond to stem cell transplantation.