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NIAID

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

National Institute of Allergy and Infectious Diseases

GATA2 Deficiency

GATA2 deficiency is a rare disorder of the 

immune system with wide-ranging effects. 

First identified in 2011, the disorder is characterized by immunodeficiency, myelodysplastic syndrome (a condition characterized 

by ineffective blood cell production), lung disease, and problems of the vascular/lymphatic 

system. GATA2 deficiency is diagnosed based 

on clinical findings, laboratory tests, and 

genetic testing. Early diagnosis is critical for 

optimal disease management, prevention of 

severe complications, treatment, and evaluation of at-risk relatives.

Genetics primer: All the cells in the body contain instructions 

on how to do their job. These instructions are packaged into 

chromosomes, each of which contains many genes. Genes are 

units of inheritance that are made up of DNA and encode proteins. 

An error, or mutation, in a gene can cause disorders such as 

GATA2 deficiency. Credit: NIAID

Genetics and Function

GATA2 deficiency is caused by germline 

mutations in the GATA2 gene. Germline 

means that the mutation is present in every 

cell in the body, not just the immune 

system cells.

The GATA2 gene produces a protein called 

a transcription factor. Transcription factors 

regulate when other genes are turned on. 

The GATA2 transcription factor helps regulate blood cell differentiation, the process by 

which blood stem cells give rise to specialized types of blood cells. When this process 

does not work properly, people are at risk 

of developing a wide range of symptoms.

Stem cells in the bone marrow produce the many types of blood 

and immune system cells through a process called differentiation. 

GATA2 helps regulate the early steps in this process. Credit: © 2007 

Terese Winslow. U.S. Govt. has certain rights.

Everyone has two copies of the GATA2

gene—one inherited from the mother and 
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one from the father. The mechanism 

underlying GATA2 deficiency is called 

“haploinsufficiency.” This means that 

having one mutated copy of GATA2

and one working copy of GATA2 is 

insufficient for normal functioning 

of the hematopoietic, or bloodmaking, system.

Many different germline GATA2

mutations have been reported. These 

can broadly be categorized as missense, 

null, and regulator mutations (see 

Glossary). Approximately 5 percent 

of people with the clinical symptoms 

of GATA2 deficiency have no detectable GATA2 mutations, suggesting 

an important role for undiscovered 

regulatory regions.

A schematic of the GATA2 gene and protein. In panel A, the five protein-coding 

parts (exons) of the gene are shown as dark boxes, and the non-protein-coding 

parts are the interspersed lines. The exons are stitched together and translated 

into the protein shown in panel B. Panel C contains an enlargement of the 

protein’s ZF-2 region. Null mutations are shown in red, regulator mutations are 

shown in blue, and missense mutations are shown in green. Credit: NIAID

Inheritance

GATA2 deficiency is inherited in an autosomal dominant 

manner, which means that a person needs only one 

abnormal GATA2 gene copy to have GATA2 deficiency. 

Dominant inheritance usually means that relatives from 

the side of the family with the mutation also have symptoms of GATA2 deficiency. These symptoms are typically 

not present at birth but develop over time. By age 20, 

about 50 percent of people with a GATA2 mutation have 

symptoms. By age 60, however, only about 5 percent of 

people remain symptom-free. This phenomenon is called 

“incomplete penetrance.”

In a family with a parent who has a GATA2 mutation, 

each child has a 50 percent, or 1 in 2, chance of inheriting 

the mutated GATA2 gene. Importantly, the chance of one 

child inheriting the mutation is independent of whether 

his or her siblings have the mutation. In other words,

if the first three children in a family have the mutation, 

the fourth child still has a 50 percent chance of inheriting 

it. Children who do not inherit the abnormal gene will not 

develop GATA2 deficiency or pass on the mutation. Often, the initial diagnosis in a family will 

initiate a cascade of genetic testing in relatives who are at risk for having inherited the mutation.

In this example, a man with an autosomal 

dominant disorder has two affected children and 

two unaffected children. Women also can pass 

on the mutation. Credit: U.S. National Library of 

Medicine
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Some GATA2 mutations are not inherited but rather arise spontaneously, or de novo, in the patient. 

De novo mutations are the result of a mutation in the parent’s sperm or egg or in the fertilized egg 

itself. Everyone is born with de novo mutations throughout their genomes, but people usually only 

find out about mutations that occur in important genes such as GATA2.

Clinical Features

Clinical features of GATA2 deficiency by organ system. Common 

clinical problems are indicated in bold. Credit: NIAID

The clinical features of GATA2 deficiency are 

wide-ranging both in type and severity. For example, one person may have severe viral infections 

causing recalcitrant warts; another may develop 

acute myeloid leukemia; and another’s only symptom may be hearing loss. This variation in how 

GATA2 deficiency manifests in each person, called 

“variable expressivity,” can be striking, even in the 

same family. Generally, the disease has a progressive course. The main clinical features of GATA2

deficiency include the following:

• Hematologic: Cytopenias, or reductions in the 

number of blood cells (cyto meaning cell, penia

meaning too few), are common and can affect 

several cell types, including B cells, natural 

killer cells, monocytes, and T cells. The results 

of this can be profound. Sometimes the problems with these cells progress to the point that 

they are formally called “myelodysplastic 

syndrome.” In a subset of patients, this can 

evolve into cancers of the blood, such as acute 

myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML). Progressively 

worsening cytopenias are associated with other 

major complications of GATA2 deficiency, 

including lung problems and infections.

• Infectious: The majority of patients with GATA2 deficiency eventually develop major viral, 

bacterial, or fungal infections. Viral infections are the most common and may include human 

papillomavirus (HPV), which causes warts; severe herpesvirus; persistent Epstein-Barr virus (EBV) 

viremia; or molluscum contagiosum (see Glossary for more details about these infections). 

• Pulmonary: The main pulmonary feature of GATA2 is the development of pulmonary alveolar 

proteinosis (PAP). This is a rare lung disease in which a type of protein builds up in the air sacs 

(alveoli) of the lungs, making breathing difficult. A subset of patients with PAP go on to develop 

a serious type of high blood pressure that affects the arteries in the lungs and heart, called 

pulmonary arterial hypertension.
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• Dermatologic: The main dermatologic symptoms are caused by the underlying immunodeficiency 

or hematologic problems. Persistent warts are the most common skin issue in people with 

GATA2 deficiency, and typically these warts are not helped by cauterization, cryotherapy, topical 

treatments, or laser treatments (see Glossary for more details). Chronic skin infections increase 

the risk of skin cancers, including squamous cell carcinoma. Skin problems due to bacteria, 

fungus, or lymph problems also have been reported in people with GATA2 deficiency.

• Neoplastic: In addition to blood cancers, solid tumors—most commonly skin cancers—also may 

occur in people with GATA2 deficiency. A number of other types of tumors have been seen, 

although their occurrence is rare and their association with the underlying GATA2 deficiency 

is unclear.

• Vascular/lymphatic: A minority of patients with GATA2 deficiency may experience chronic 

lymphedema, swelling in an arm or leg caused by a lymphatic system blockage. 

• Other: Hearing loss, increased risk of miscarriage, and hypothyroidism also may be part of the 

clinical spectrum of GATA2 deficiency.

Because GATA2 deficiency is a rare disorder, current knowledge is based on the careful study of 

several dozen families affected by GATA2 deficiency. As research continues, understanding of the 

clinical spectrum, disease course, and underlying biology will be refined.

Laboratory Findings

Laboratory findings can vary widely in this disease, although they typically include low levels of 

certain blood cells, especially B cells, natural killer cells, monocytes, and dendritic cells.

Management and Treatment

Treatment for GATA2 deficiency is 

based on a person’s clinical condition 

and may include medications and 

other strategies for managing specific 

infections, cytopenias, and pulmonary or vascular issues. Doctors 

may recommend the prophylactic, 

or preventive, use of antimicrobial 

drugs to prevent infections.

Illustration depicting a bone marrow, or hematopoietic stem cell, transplant. 

Credit: © 2011 Terese Winslow LLC. U.S. Govt. has certain rights.

A bone marrow transplant, also 

called a hematopoietic stem cell 

transplant, is the best long-term 

treatment option for many serious genetic immunodeficiency diseases. This therapy has been used 

to manage patients with GATA2 deficiency, and it can resolve most of their clinical symptoms and 

laboratory abnormalities. In this procedure, stem cells are removed from a donor, the patient receives 

treatment to destroy his or her own blood-forming cells, and then the patient receives the donor’s 
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stem cells. The transplanted stem cells form a new, healthy immune system. Unfortunately, bone 

marrow transplantation poses substantial risks. These include graft-versus-host disease, in which the 

transplanted cells recognize the recipient’s cells as “foreign” and attack them; graft failure, in which 

the recipient’s immune system rejects the transplant; and complications from the chemotherapy prior 

to transplant, such as infertility. Families must carefully consider the risks and benefits before 

pursuing bone marrow transplant or other treatment options.

GATA2 Deficiency and Your Family

Living with GATA2 deficiency can be difficult not only for the person who has it but also for their 

family members. It is important for families to talk openly about GATA2 deficiency and about how the 

family is dealing with it so misconceptions can be corrected and children can learn to cope with their 

reactions. Some children with GATA2 deficiency have to work hard to develop their self-confidence 

and sense of security. Everyone needs to be reminded that they have many positive characteristics, 

especially when their appearance attracts attention.

Some children who have siblings with GATA2 deficiency worry about their brother or sister being 

in pain or dying from the disease. Some think that they may develop symptoms because they look or 

act like a sibling who has the disease or that the disease is contagious. Some children struggle with 

how much time their parents spend with their sick sibling. Many families benefit from meeting or 

talking to other families affected by the same rare disease. Patient organizations such as the Immune 

Deficiency Foundation (www.primaryimmune.org) or Be The Match (www.bethematch.org), operated 

by the National Marrow Donor Program, are great resources for providing useful information and 

support. Counseling also can help families cope with the challenges of GATA2 deficiency.

At the same time, many families say that GATA2 deficiency has brought them closer together. 

Through their experiences with the disease and its treatment, family members learn about controllable 

and uncontrollable aspects of life. How a family responds to the stress of any illness is controllable 

and an important aspect of managing GATA2 deficiency. Children also learn who they can turn to 

for support and how to solve problems. Acknowledging both the challenges and opportunities that 

GATA2 deficiency presents helps everyone develop resilience.
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Glossary

Acute myeloid leukemia (AML)—A type of cancer of the blood 

and bone marrow that affects immature blood cell growth.

Bone marrow transplant—A procedure to replace unhealthy or 

defective bone marrow with healthy bone marrow stem cells. 

Bone marrow is the soft, fatty tissue inside bones. Also called 

hematopoietic stem cell transplant.

Cauterization—A procedure in which warts are destroyed by 

burning them in a controlled way.

Chronic lymphedema—Swelling in an arm or leg caused by a 

lymphatic system blockage.

Chronic myelomonocytic leukemia (CMML)—A type of cancer 

of the blood that tends to progress more slowly than acute 

forms of leukemia.

Cryotherapy—A procedure in which warts are destroyed by 

freezing them in a controlled way.

Cytopenia—A reduction in the number of blood cells, which can 

take many forms depending on the population of cells affected. 

De novo mutations—Mutations that are not inherited but new 

in the patient as a result of a mutation in their parent’s sperm 

or egg or in the fertilized egg itself.

Dermatologic—Related to conditions of the skin.

Differentiation—The process by which cells become progressively more specialized.

Epstein-Barr virus (EBV) viremia—EBV is a very common virus 

that can remain in the body indefinitely in its latent form. Viremia 

is the presence of the virus in the blood. EBV viremia can signal 

broader problems with the immune system.

Gene—A unit of heredity that is transferred from parent to child. 

Genes are made up of DNA and encode proteins.

Germline mutations—A mutation that is present in every cell in 

a person’s body, not just the immune system cells. 

Haploinsufficiency—Indicates that having a single working 

copy of a gene is not sufficient to produce enough protein to 

be free from the gene-associated disease.

Hematologic—Related to the blood system.

Hematopoietic system—The system of organs and tissues, 

primarily the bone marrow, spleen, tonsils, and lymph nodes, 

that are involved in the production of blood and immune cells.

Herpesvirus—A large family of viruses that can cause disease.

Human papillomavirus (HPV)—A common virus that can cause 

warts.

Hypothyroidism—A condition in which the thyroid gland, an 

endocrine gland at the base of the neck that helps regulate 

metabolism, does not produce enough thyroid hormone.

Immune system—A system of biological structures and processes within the body that protects it against “foreign” threats 

such as bacteria or viruses.

Immunodeficiency—A state in which the immune system’s 

ability to fight disease is compromised or entirely absent.

Incomplete penetrance—Penetrance refers to the degree to 

which a particular variant of a gene is expressed in a population. Incomplete penetrance means that not everyone who 

carries the variant expresses the trait.

Lymphatic system—The network of vessels though which 

lymph drains from the tissues into the blood.

Missense mutation—A type of mutation in which a single 

nucleotide change results in a change in an amino acid. Amino 

acids are the building blocks of proteins.

Molluscum contagiosum—A chronic viral skin disease characterized by groups of small, smooth, painless pinkish bumps 

on the skin with central depressions that yield a milk-like fluid 

when squeezed.

Myelodysplastic syndrome—A diagnostic term that refers to 

a group of disorders caused by poorly formed or dysfunctional 

blood cells.

Neoplastic—Related to an abnormal growth of tissue, benign 

or malignant.

Null mutation—A type of mutation that results in the complete 

lack of the normal function of the gene. 

Pulmonary—Related to the lungs.

Pulmonary alveolar proteinosis (PAP)—A rare lung disease in 

which a type of protein builds up in the air sacs (alveoli) of the 

lungs, making breathing difficult.

Regulatory mutations—A type of mutation that affects the 

regulation of the gene.

Squamous cell carcinoma (SCC)—A type of cancer caused by 

an uncontrolled growth of an abnormal squamous cell. SCC 

can develop from many organs but is often a skin cancer. 

Stem cells—Cells that are capable of giving rise to several 

different cell types.

Transcription factor—A protein that regulates when other 

genes are turned on. 

Vascular system—A system of vessels that carry blood and 

lymph through the body, delivering oxygen and nutrients and 

taking away waste. Also called the circulatory system.

September 2016

www.niaid.nih.gov