MonoMAC syndrome is a rareautosomal dominant syndrome associated with:monocytopenia,B andNK celllymphopenia; mycobacterial, viral, fungal, and bacterialopportunistic infections; andvirus infection-induced cancers. The disorder often progresses to the development ofmyelodysplasia,myeloid leukemias, and other types of cancer. MonoMAC is a life-threatening andprecancerous disorder.^[1][2]

Inactivating mutations in one of the two parentalGATA2genes is responsible for the many diverse presentations of agenetic disorder that groups these presentations together into a single disease termedGATA2 deficiency. Theseautosomal dominant mutations are known or presumed to cause a reduction, i.e. ahaploinsufficiency, in the cellular levels of the gene's product,GATA2. The GATA2protein is atranscription factor critical for theembryonic development, maintenance, and functionality ofblood-forming,lympathic-forming, and other tissue-formingstem cells. In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, and/or other disorders that may begin as apparently benign abnormalities but commonly progress to severe organ (e.g. lung) failure, enhanced susceptibility toopportunistic infections,virus infection-induced cancers, themyelodysplastic syndrome, and/or various types ofleukemia. MonoMAC is a presentation of GATA2 deficiency that involves primarily signs and symptoms of immune deficiency that cause an extremely high susceptibility to infections and infection-induced benign and malignant tumors. In addition to this, however, MonoMAC-afflicted individuals often show one or moresigns and symptoms of other GATA2 presentations.^[3][4]

MonoMAC was first described by Vihn and colleagues in 2010 as anautosomal dominant familial disease.^[5] One year later, Dickinson and colleagues discovered that the MonoMAC disorder in four individuals was associated with any one of four different mutations in theGATA2 gene.^[6] Subsequent studies identified numerous otherGATA2 gene mutations that are associated with the development of MonoMAC, showed that these mutations inactivated or were considered likely to inactivate one of two parentalGATA2 genes, and found that essentially all individuals with MonoMAC had one of the mutations known or considered to inactivateGATA2.^[3]

This syndrome is characterized by an increased susceptibility to disseminated nontuberculous mycobacterial infections, viral infections, especially with humanpapillomaviruses, and fungal infections, primarily histoplasmosis, and molds. There is profound monocytopenia, B lymphocytopenia and NK lymphocytopenia. Patients have an increased chance of developing malignancies, including:myelodysplasia/leukemiavulvar carcinoma,metastatic melanoma,cervical carcinoma,Bowen disease of the vulva, and multipleEpstein–Barr virus(+)leiomyosarcoma. Patients may also developpulmonary alveolar proteinosis without mutations in thegranulocyte-macrophage colony-stimulating factor receptor or anti-granulocyte-macrophage colony-stimulating factor autoantibodies. Last, patients may develop autoimmune phenomena, includinglupus like syndromes,primary biliary cirrhosis or aggressivemultiple sclerosis.^{[citation needed]}

Of the 26, now 28, patients probably afflicted by this syndrome, 48% died of causes ranging fromcancer tomyelodysplasia with a mean age at death of 34.7 years and median age of 36.5 years.

12 distinct mutations in the GATA2 gene have been identified. They include missense mutations affecting the zinc finger-2 domain and insertion/deletion mutations leading to frameshifts and premature termination.^{[citation needed]}

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Bone marrow transplants are currently the only treatment.^{[citation needed]}

• Primary immunodeficiency
• Genetic disorder

• Immunodeficiency
• Syndromes
• Autosomal dominant disorders
• Immune system disorders
• Transcription factor deficiencies

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