MonoMAC
| monoMAC syndrome | |
|---|---|
| Classification and external resources |
The autosomal dominant syndrome associated with monocytopenia, B and NK cell lymphopenia and mycobacterial, fungal and viral infections (abbreviated MonoMAC) is a rare genetic disorder first described by Vihn and colleagues in 2010[1] and is associated with myelodysplasia, cytogenetic abnormalities, pulmonary alveolar proteinosis and myeloid leukemias.[2] Multiple mutations in the GATA2 are considered to be responsible for this syndrome.
Signs and symptoms
This syndrome is characterized by an increased susceptibility to disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, 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/leukemia vulvar carcinoma, metastatic melanoma, cervical carcinoma, Bowen disease of the vulva, and multiple Epstein-Barr virus(+) leiomyosarcoma. Patients may also develop pulmonary alveolar proteinosis without mutations in the granulocyte-macrophage colony-stimulating factor receptor or anti-granulocyte-macrophage colony-stimulating factor autoantibodies. Last, patients may develop autoimmune phenomena, including lupus like syndromes, primary biliary cirrhosis or aggressive multiple sclerosis.
Of the 26, now 28, patients probably afflicted by this syndrome, 48% died of causes ranging from cancer to myelodysplasia with a mean age at death of 34.7 years and median age of 36.5 years.
| Clinical feature | Overall (%) | Autosomal dominant patients (%) | Sporadic patients (%) |
|---|---|---|---|
| Infection | |||
| Mycobacteria | 78 | 86 | 73 |
| HPV | 78 | 86 | 73 |
| Fungi | 28 | 43 | 18 |
| Complication | |||
| PAP | 33 | 29 | 36 |
| Panniculitis/erythema nodosum | 33 | 29 | 36 |
| Myelodiysplasia/acute myeloid leukemia | 50 | 71 | 36 |
| Death | 28 | 43 | 18 |
Genetics
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.
Treatment
Bone Marrow Transplants are currently the only treatment.
See also
References
- ↑ Vinh DC, Patel SY, Uzel G, Anderson VL, Freeman AF, Olivier KN, Spalding C, Hughes S, Pittaluga S, Raffeld M, Sorbara LR, Elloumi HZ, Kuhns DB, Turner ML, Cowen EW, Fink D, Long-Priel D, Hsu AP, Ding L, Paulson ML, Whitney AR, Sampaio EP, Frucht DM, DeLeo FR, Holland SM (Feb 2010). "Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia". Blood. 115 (8): 1519–29. doi:10.1182/blood-2009-03-208629. PMC 2830758
. PMID 20040766. - ↑ Hsu AP, Sampaio EP, Khan J, Calvo KR, Lemieux JE, Patel SY, Frucht DM, Vinh DC, Auth RD, Freeman AF, Olivier KN, Uzel G, Zerbe CS, Spalding C, Pittaluga S, Raffeld M, Kuhns DB, Ding L, Paulson ML, Marciano BE, Gea-Banacloche JC, Orange JS, Cuellar-Rodriguez J, Hickstein DD, Holland SM (Jun 2011). "Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome". Blood. 118 (10): 2653–5. doi:10.1182/blood-2011-05-356352. PMID 21670465.