GATA2 deficiency syndrome

GATA2 is a gene that acts like a master switch for making blood cells. When one copy does not work, the marrow struggles to make certain white cells. People often have very few monocytes, B cells, natural killer cells and dendritic cells, which are cells that help find and fight germs.

Doctors once described several separate illnesses that turned out to share this cause. MonoMAC syndrome means low monocytes with serious mycobacterial infections. DCML deficiency describes the missing cell types. Emberger syndrome combines lymphedema, a long-lasting swelling from poor lymph drainage, with a risk of leukemia.

Today these are seen as one condition with many faces. Some people first learn they have it when they are diagnosed with MDS. Others learn it after years of unusual infections, or after a relative is diagnosed.

The cause is a change in one of the two copies of the GATA2 gene. One changed copy is enough to cause the condition. The change may be passed down from a parent, or it may appear for the first time in the person.

A parent with the change has a 50% chance of passing it to each child. But the condition does not look the same in every family member. People with the very same gene change can have very different health, and some have no symptoms for many years. Genetic counseling can help a family understand testing and what a result means.

The most common problems are infections and changes in the bone marrow. Infections can include mycobacteria (germs related to the one that causes tuberculosis), fungi and human papillomavirus (HPV), which can cause widespread warts and precancer of the genital area. Some people develop a lung condition called pulmonary alveolar proteinosis, in which a protein-rich material fills the air sacs. Others have lymphedema or hearing loss that was present from birth.

Over time the marrow often makes fewer cells, and the lifetime chance of MDS or AML is high. According to NCI, the median age at diagnosis of these blood cancers is 17 years, but they have been found in young children and in people in their late 70s. A marrow change called monosomy 7, the loss of one copy of chromosome 7, is common, especially in children, and is linked to faster progression.

Early signs that the marrow is getting worse often do not show up in routine blood counts. That is why doctors often check the marrow itself, with genetic tests of the marrow cells, on a regular schedule.

Many people are diagnosed as teens or adults, sometimes after years of infections that no one could explain. The diagnosis can bring relief and fear at once. It also raises new questions for parents, brothers, sisters and children, who may choose to be tested.

Living with it often means frequent blood tests, marrow exams and visits to several specialists. Deciding whether and when to have a transplant can be very hard when a person feels mostly well. A transplant then brings conditioning treatment, weeks in or near the hospital and months of follow-up for infections and graft-versus-host disease.

A transplant needs healthy blood-forming cells from a donor with a close HLA match. Family members are tested for the family’s GATA2 change before they can donate, even if they feel well and have normal blood counts. NCI notes that MDS and AML have been reported to grow from donated cells in families with GATA2 deficiency.

Because relatives may share the gene change, many people need an unrelated donor. In the European study of 65 children and teens, 40 received cells from an unrelated donor. In one NIH study of 22 transplants, 13 used matched unrelated donors. Half-matched family donors and cord blood have also been used.

Finding the diagnosis early gives time to test the family and search the registry before the marrow changes. New registry members widen the choices for people with this condition, though joining cannot promise a match for any one person.