The GATA2 mutation has been found to underlie at least 5 previously described conditions that are now recognized as phenotypic variants of the same genetic disorder. Specifically, these include monocytopenia and Mycobacterium avium complex infection (MonoMAC) syndrome; dendritic cell, monocyte, B and NK lymphoid deficiency; familial myelodysplastic syndrome / acute myeloid leukemia; Emberger syndrome (primary lymphedema with myelodysplasia); and classical NK-cell deficiency. As these names suggest, GATA2 deficiency causes a primary immunodeficiency associated with disseminated opportunistic infections and lymphoproliferative disorders.
Affected patients are at increased risk for multiple infections including nontuberculous mycobacteria, disseminated opportunistic and invasive fungi, and severe / recalcitrant herpesvirus and papillomavirus disease. Over half of all patients will develop myelodysplastic syndrome, with a smaller proportion going on to develop acute myeloid leukemia or chronic myelomonocytic leukemia. Multiple cutaneous malignancies have also been described, typically those associated with a viral pathogenesis such as human papillomavirus-associated squamous cell carcinoma, Merkel cell carcinoma (Merkel cell polyomavirus), and Epstein-Barr virus-positive smooth muscle tumors.
D84.9 – Immunodeficiency, unspecified
414393003 – Hereditary disorder of cellular component of blood
Differential Diagnosis & Pitfalls
- Human immunodeficiency virus (HIV) infection – Should be excluded given that disseminated atypical mycobacterial and opportunistic fungal infections are well known to occur in patients with advanced HIV/AIDS.
- Severe combined immunodeficiency disease – Heterogenous group of disorders resulting in severe dysfunction of T and B cells. Diagnosis made on direct gene analysis.
- Myelodysplastic syndrome – May occur secondary to many exposures such as radiation, alkylating chemotherapeutic agents, or genetic conditions (eg, Fanconi anemia).
- Ataxia telangiectasia – Similar to GATA2 deficiency, gene mutations also predispose to sinopulmonary infections, Epstein-Barr virus viremia, and increased risk for malignancies.
- Wiskott-Aldrich syndrome – X-linked recessive disease affecting males almost exclusively. Manifests as persistent atopic dermatitis, increased susceptibility to infections (viral and bacterial), and thrombocytopenia.