Hyper IGM (CD40L-deficient)

What is hyper IGM (CD40L-deficient)?

Hyper IgM (HIGM) syndrome (CD40L-deficient) is a rare immune disorder in which a child’s body doesn't produce certain disease-fighting antibodies. It is a primary immunodeficiency disease, which means it is inherited and present at birth.

What are the different types of hyper IGM (CD40L-deficient)?

There are two main types of hyper IgM

1. X-linked hyper IgM (XHIM) is the most common type and only affects boys.

2. Autosomal recessive hyper-IgM syndrome (ARHIM) can affect both boys and girls.

What are the signs and symptoms of hyper IGM (CD40L-deficient)?

Children with HIGM are more susceptible to infections, have infections that won't go away or have recurrent severe infections. A child with HIGM is also more susceptible to certain cancers, including liver cancer.

Symptoms of HIGM in children include:

• Frequent, hard to treat infections

• Chronic diarrhea

• Recurrent ear or eye infections, sinusitis, skin infections or pneumonia

• Enlargement of the lymph nodes, tonsils, spleen or liver

• An autoimmune blood disorder such as neutropenia, which is an unusual drop in a certain kind of white blood cell

If your child is a boy and has recurrent, severe infections or doesn't respond well to treatments, see a doctor.

How is hyper IGM (CD40L-deficient) diagnosed?

Hyper IgM (HIGM) syndrome is a disorder in which a child's immune system produces too many IgM antibodies while not producing any IgG antibodies. The result is that children can't fight off certain types of infections. Boys account for more than 70 percent of cases of HIGM, as the defective gene that causes the more common XHIM form attaches to the X chromosome.

Your child's doctor will begin a diagnosis by asking about your child’s medical history and performing a physical examination. If he suspects HIGM, he will send blood samples to a specialized lab for DNA testing. DNA tests confirm HIGM by analyzing the genes known to cause the disorder.

What are the causes of hyper IGM (CD40L-deficient)?

Due to the mutation, a child with HIGM produces too much of the IgM antibody and none of the IgG antibody. A mother with the defective gene will pass XHIM - the most common form of the disorder - to a male child.

How is hyper IGM (CD40L-deficient) treated?

In most cases, hyper IgM (HIGM) syndrome shows up in infancy. Nearly all cases are diagnosed by the time a child reaches 4 years of age. With proper treatment, children with HIGM can go on to lead normal, healthy lives.

The most common treatment for HIGM is intravenous immunoglobulin (IVIG) therapy. Children receiving this treatment get regular infusions of donated blood plasma to prevent infections. In boys with XHIM, IVIG replaces missing IgG antibodies while normalizing levels of IgM. Your child will receive IVIG infusions every three or four weeks for life. The treatments can be administered either at home or in an outpatient clinic. IVIG is the only effective treatment for ARHIM.

Other treatments include:

• Antibiotics - Boys with XHIM are often given antibiotics to prevent certain types of pneumonia.

• G-CSF (Neupogen®**)** - Injections of G-CSF stimulate production of neutrophils in patients with neutropenia.

• Bone marrow transplant - Bone marrow transplants can cure XHIM in some patients with a life-threatening form of the disease. Siblings are usually the best donors, but a parent can be a good candidate as well. In rare cases, an unrelated donor can be used.

• Cord blood stem cell transplantation - Another treatment for HIGM is to use stem cells from cord blood. Stem cells from blood in a baby's umbilical cord or placenta can be acquired immediately after delivery. Cord blood from a healthy sibling may be used to help cure a child with XHIM.