NORD - WHIM Syndrome

WHIM syndrome is a rare primary immunodeficiency disorder, which means the body’s immune system doesn’t function properly, so individuals are more susceptible to infections caused by viruses and bacteria.

Components of the blood develop in the bone marrow, which is the spongy center of some bones. When they are mature, they move into the blood and circulate around the body. Some of these cells, called white blood cells, are part of the immune system and fight against infections. And there are several types that have their own specialized functions. These include neutrophils and monocytes which are important in the initial infection response; T lymphocytes, called T cells which help regulate the immune response; and B lymphocytes, called B cells, which secrete antibodies. Antibodies are also called immunoglobulins and are abbreviated as Ig. They are proteins that coat viruses and bacteria, and either kill them or help white blood cells find them. In WHIM syndrome, neutrophils and other immune cells don’t move out of the bone marrow efficiently. So, they are not present in high levels in the blood to fight infections.

Now, WHIM syndrome is an acronym for the common signs and symptoms of the disorder. But not all individuals will experience them or to the same severity. Warts are caused by a common virus called human papillomavirus, abbreviated HPV. Warts are most commonly found on the hands and feet, but occasionally also on the arms and legs as well as the face. They may also be found both externally and internally at the anus or genitals, where some can develop into cancer. Hypogammaglobulinemia means fewer antibodies are present in the blood caused by the low levels of B cells in the blood. But low levels of T cells, and especially neutrophils are seen. Bacterial infections can begin at an early age and may be chronic or recurring. These infections can happen anywhere in the body, but commonly involve the skin; ears, sinuses, mouth, lungs, joints and bones; and urinary tract. Sometimes these lead to more serious complications, like impaired function and in severe cases, death. Finally, Myelokathexis refers to the unusually high levels of white blood cells trapped in the bone marrow, particularly neutrophils.

WHIM syndrome is caused by changes, or mutations, in the CXCR4 gene. This gene provides the instructions to make a protein called a chemokine receptor, which is on the surface of most white blood cells. Typically, it helps the cell move around the body. In WHIM syndrome, the mutation increases the activity of the receptor and prevents the cell’s proper movement, like leaving the bone marrow. A CXCR4 gene mutation can occur without a family history of WHIM syndrome, but usually it’s inherited from a parent. WHIM syndrome is an autosomal dominant disorder, which means inheriting just one copy of the mutation is enough for an individual to be affected.

Diagnosis of WHIM syndrome can be based on an individual’s symptoms and medical history, like recurrent infections, and family history of the disorder. A few clinical tests are especially important, like a blood test called a complete blood count with differential. This test typically shows low levels of cells circulating in the blood, especially neutrophils. Another type of test called bone marrow biopsy is a way of actually seeing the high numbers of white blood cells in the bone marrow. And finally, a genetic test to identify a mutation in the CXCR4 gene can confirm the diagnosis.