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 25 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 features and complications of the syndrome

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

There is no FDA approved treatment. Stem cell transplantation is currently under evaluation.^[3]

See also

• Primary immunodeficiency
• Genetic disorder

References

1. ^ 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. http://bloodjournal.hematologylibrary.org/content/early/2011/06/13/blood-2011-05-356352.long. 
2. ^ 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 [Epub ahead of print]. doi:10.1182/blood-2011-05-356352. PMID 21670465. http://bloodjournal.hematologylibrary.org/content/early/2011/06/13/blood-2011-05-356352.long. 
3. ^ National Institutes of Health Clinical Center (April 2011). "Pilot and Feasibility Study of Reduced-Intensity Hematopoietic Stem Cell Transplant for MonoMAC". ClinicalTrials.gov. http://clinicaltrials.gov/ct2/show/NCT00923364. Retrieved 17 July 2011.