GATA2 deficiency is a germline disease which causes a wide spectrum of phenotypes including viral and bacterial infections, cytopenias, myelodysplasia, myeloid leukemias, pulmonary alveolar proteinosis and lymphedema. The age of clinical presentation ranges from early childhood to late adulthood, with most occurring in adolescence to early adulthood. We review the expanding GATA2 deficient phenotype, molecular genetics of disease, and developments in treatment.

GATA2 mutations have been found in up to 10% of those with congenital neutropenia and/or aplastic anemia. Heterozygous mutations appear to cause haploinsufficiency due either to protein dysfunction or uniallelic reduced transcription. Disease-associated mutations in intronic regulatory elements or variations within the 5’ leader exons indicate that regulation of GATA2 is critical. Those with GATA2 mutations are at high risk for myelodysplasia (MDS), cytogenetic abnormalities, acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML). Bone marrow transplantation has been successful for both hematopoietic and pulmonary alveolar proteinosis repair.

GATA2 is a zinc finger transcription factor essential for embryonic and definitive hematopoiesis as well as lymphatic angiogenesis. GATA2 deficiency is caused by a variety of mutations in the GATA2 gene and can have variable presentation, onset and outcome. Patients are susceptible to mycobacterial, viral and fungal infections and can develop MDS, acute or chronic leukemias, lymphedema and pulmonary alveolar proteinosis. Hematopoietic stem cell transplantation (HSCT) reverses most of the clinical phenotype with good long-term outcomes.