HYPER IgM SYNDROME
Dr Ira Shah
Consultant Pediatrician, Nanavati Hospital and B.J.Wadia Hospital for Children, Mumbai
Editor - Pediatric Oncall
What is hyper IgM syndrome?
Our body produces various types of antibodies from the B-lymphocytes. These antibodies help to fight infection. The antibodies are IgA, IgD, IgE, IgM & IgG. Usually with infections the initial antibody to form is IgM which then switches to IgG, IgA or IgE. In patients with hyper IgM (HIM) syndrome, there is inability to switch IgM to IgG, IgA or IgE type. Thus patients are susceptible to infections.
Why does the switch of IgM to other antibodies does not occur in Hyper IgM syndrome?
B-lymphocytes can produce IgM antibodies on their own but they require help from T-lymphocytes to switch antibody production. Various genetic defects affect this interaction leading to Hyper IgM. Most common defect is decreased production in the ?CD40 ligand? protein on the surface of T-lymphocytes. Thus the B-lymphocytes protein CD40 cannot bind to this protein and thus switch does not occur. The genetic mutation leading to defect in CD40 ligand is in the gene located on the X-chromosome and Hyper IgM syndrome due to CD40 ligand defect is seen in boys.
Sometimes the CD40 on B-lymphocytes does not function properly and that can also lead to Hyper IgM syndrome. This type of Hyper IgM can affect both boys and girls.
Hyper IgM syndrome may be associated with skin problem such as sparse hair and conical teeth (called as ectodermal dysplasia) due to defect in another gene located on the X-chromosome that affects function of NF-KB molecule. Again boys are affected by this genetic mutation.
What the symptoms of Hyper IgM syndrome?
Most patients with Hyper IgM have clinical presentations within first 2 years of life. Symptoms of HIM include recurrent upper and lower respiratory tract infections. Infections due to PCP, cytomegalovirus, fungal such as cryptococcus are common. The type of Hyper IgM affecting both boys and girls also leads to enlarged tonsils, liver, spleen and lymphnodes. Autoimmune disorders are common in children with Hyper IgM syndrome. Cryptosporidium infection can lead to diarrhea and sclerosing cholangitis (a form of liver disease).
How is the diagnosis of Hyper IgM syndrome made?
Diagnosis of Hyper IgM syndrome is suspected in patients with low or absent IgG or IgA and normal or elevated IgM antibodies. In boys, failure to express CD40 ligand on T-cells can be demonstrated. Genetic tests to detect specific mutations can be done in specialized laboratories. About half the patients may have low neutrophil count.
What is the treatment of Hyper IgM syndrome?
Immunoglobulin replacement therapy helps to decrease number of infections in patients with Hyper IgM. Cotrimoxazole antibiotic can be used as preventive measure to prevent PCP pneumonia. Patients should drink boiled and filtered water to prevent infection by cryptosporidium.
The curative treatment consists of bone marrow transplantation or cord blood stem cell transplantation.
Can Hyper IgM syndrome be diagnosed in the fetus?
If the mutation causing Hyper IgM is known in a given family, the prenatal diagnosis in a male fetus in form of checking the mutation in the amniotic cells or chorionic villus cells can be done to see if the fetus is carrying the defective gene or not.
Last Updated: 1st August 2011