We’ve gotta recognize GATA2 deficiency
By Warren R. Heymann, MD
Dec. 26, 2018
I’ll begin with my conclusion — dermatologists need to recognize patients with GATA 2 deficiency because it can be successfully treated with hematopoietic stem cell transplantation (HSCT).
GATA2 deficiency is a germline disease with a wide phenotypic spectrum including viral and bacterial infections, cytopenias, myelodysplasia, myeloid leukemias, pulmonary alveolar proteinosis and lymphedema. The disorder presents later than other classical immunodeficiencies, appearing in older children or adults. The inheritance pattern is autosomal dominant, although there are a large number of sporadic cases. (1)
According to Spinner et al; “In 2011, heterozygous mutations in the hematopoietic transcription factor GATA2 were identified as the cause of 4 previously described clinical syndromes: monocytopenia and mycobacterial infections syndrome; dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency; familial myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) and Emberger syndrome (primary lymphedema with MDS)…These syndromes are now recognized as different manifestations of a single genetic disorder with protean disease manifestations. More recently, GATA2 mutations have been identified in additional clinical cohorts including pediatric neutropenia, aplastic anemia, and the original case report of human NK cell deficiency.” (2)
The guanine‐adenine‐thymine‐adenine (GATA)‐binding protein family of transcription factors comprises six proteins (GATA 1–6), which are involved in a variety of physiological and pathological factors. GATA binding proteins 1–3 are required for differentiation of mesoderm‐ and ectoderm‐derived tissues, including hematopoietic stem cells and the central nervous system. GATA2 is a zinc finger transcription factor acting as a key regulator of haematopoiesis; it is required for development and maintenance of a healthy stem‐cell pool. (3)
Up to 70% of patients with GATA2 mutations demonstrate dermatological features, mainly genital or extragenital warts, panniculitis or erythema nodosum and lymphoedema. (Please see the addendum for a list of dermatological manifestations of GATA2 deficiency.) Polat et al reported three patients presenting with common dermatological and hematological features leading to the diagnosis of GATA2 deficiency, but also with skin manifestations that have not been previously described: gingival hypertrophy, macroglossitis, and granulomatous lupoid facial lesions. One of the three patients, a 20 year-old woman (with pancytopenia, recurrent ENT infections, labial herpes, verrucae, and facial noninfectious lupoid lesions with a granulomatous histology) was treated with allogeneic stem cell transplantation. Five months later she no longer had infections, the skin lesions resolved, and the pancytopenia resolved. Interestingly, a few months after the HSCT lymphedema of the lower extremities was observed. (4)
Although there are no clear guidelines for managing GATA2 deficiency, the following have been recommended: 1) vaccination of children against HPV; 2) being vigilant for HSV infection; 3) using azithromycin prophylaxis to prevent mycobacterial and routine bacterial infections; 4) monitoring complete blood counts every 3 to 6 months and bone marrow biopsy with cytogenetics every 1 to 2 years and considering HSCT prior to any transition to severe myelodysplasia or leukemia.(1); and 5) performing biopsies on any rapidly changing or painful lesions, especially of the head, neck, and genital regions, because of the risk of squamous cell carcinomas related to HPV dysplasia. (5)
Point to remember: Extensive and recalcitrant verrucae, associated with a history of multiple infections and lymphedema, should alert dermatologists to consider the diagnosis of GATA2 deficiency.
Dermatological Manifestations of GATA2 deficiency (from references 3 and 4):
Warts (genital and extragenital)
Herpes virus infections
Nontuberculous mycobacterial infections
Intraepithelial Bowenoid papulosis (HPV‐related)
Basal cell carcinoma
Squamous cell carcinoma
Sweet syndrome associated with myelodysplasia/acute myeloid leukemia
Granulomatous facial lesions
1. Hsu AP, et al. GATA2 Deficiency. Curr Opin Allergy Clin Immunol 2015; 15: 104-9.
2. Spinner MA, et al. GATA2 deficiency; A protean disorder of hematopoiesis, lymphatics, and immunity. Blood 2014; 123: 809-21.
3. Nanda A. Spectrum of cutaneous manifestations among patients with GATA2 deficiency. Br J Dermatol 2018; 178: 583-94.
4. Polat A. Skin manifestations among GATA2-deficient patients. Br J Dermatol 2018; 178: 781-5.
5. Muszynski MA, et al. A woman with warts, leg swelling, and deafness. J Am Acad Dermatol 2014; 71: 577-80.
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