The autosomal dominant syndrome associated with monocytopenia

Monocytopenia

Monocytopenia is a form of leukopenia associated with a deficiency of monocytes. The causes of monocytopenia include: acute infections, stress, treatment with glucocorticoids, aplastic anemia, hairy cell leukemia, acute myeloid leukemia, treatment with myelotoxic drugs and genetic syndromes.It has...

, B

B cell

B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

 and NK cell lymphopenia and mycobacterial, fungal and viral infections (abbreviated MonoMAC) is a rare genetic disorder

Genetic disorder

A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....

 first described by Vihn and colleagues in 2010 and is associated with myelodysplasia, cytogenetic abnormalities, pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis is a rare lung disease in which abnormal accumulation of surfactant occurs within the alveoli, interfering with gas exchange. PAP can occur in a primary form or secondarily in the settings of malignancy , pulmonary infection, or environmental exposure to dusts or...

 and myeloid leukemia

Myeloid leukemia

Myeloid leukemia is a type of leukemia affecting myeloid tissue.Types include:* Acute myeloid leukemia* Chronic myelogenous leukemia...

s. Multiple mutations in the GATA2

GATA2

GATA binding protein 2, also known as GATA2, is a human gene. The protein encoded by this gene is a transcription factor.The GATA family of transcription factors, which contain zinc fingers in their DNA binding domain, have emerged as candidate regulators of gene expression in hematopoietic cells...

 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

Leukemia

Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

 vulvar carcinoma, metastatic melanoma

Melanoma

Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...

, cervical carcinoma, Bowen disease of the vulva, and multiple Epstein-Barr virus

Epstein-Barr virus

The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...

(+) leiomyosarcoma

Leiomyosarcoma

Leiomyosarcoma , aka LMS, is a malignant cancer of smooth muscle....

. Patients may also develop pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis is a rare lung disease in which abnormal accumulation of surfactant occurs within the alveoli, interfering with gas exchange. PAP can occur in a primary form or secondarily in the settings of malignancy , pulmonary infection, or environmental exposure to dusts or...

 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

Lupus

Lupus most commonly refers to the disease systemic lupus erythematosus.Lupus may also refer to:-Medicine:* Lupus erythematosus, a chronic autoimmune disease with several different forms...

 like syndromes, primary biliary cirrhosis

Primary biliary cirrhosis

Primary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring,...

 or aggressive multiple sclerosis

Multiple sclerosis

Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

.

Of the 25 patients probably afflicted by this syndrome, 48% died of causes ranging from cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 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.