Chronic granulomatous disease

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What is chronic granulomatous disease?

Chronic granulomatous disease (CGD) is a very rare disorder, estimated to occur 1 in every 200,000 people. The disorder affects the way neutrophils, a type of white blood cell, work. Neutrophils "eat" germs (bacteria and fungi) and then use special proteins, called enzymes, to kill them. Neutrophils from children with CGD "eat" the bacteria and fungi but cannot kill them. This is because children with CGD are born without one or more of the killing enzymes in their neutrophils. The rest of their immune system functions normally.

Children with CGD may have one or more of the following:

Individuals with CGD are usually healthy at birth, but go on to develop recurrent infections, infections, which are often difficult to treat or infections caused by unusual organisms, such as fungi, in the first few months or years of life. Although infection of any organ system or tissue in the body can occur, the places in the body affected most are the skin, lungs, lymph nodes, liver and bones. Typical infections include:

  • Abscesses of the skin, liver or lymph nodes
  • Osteomyelitis (infection of the bone)
  • Recurrent pneumonias

Five organisms are responsible for the majority of infections in CGD. These include

  • Staphylococcus aureus, Burkholderia cepacia, Serratia marcescens (types of bacteria)
  • Nocardia species, Aspergillus species (types of fungi)

Individuals with CGD often have gingivitis (recurrent bleeding gums), and tend to have poor wound healing. Good dental hygiene is therefore very important in those with CGD.

How do you get CGD?

CGD is an inherited disease. You do not catch it, you are born with it. Most children with CGD (4 of every 5) are boys. The disease occurs because the affected gene, which tells neutrophils how to kill organisms, has a mistake in it (mutation) and doesn't work properly. The gene for one type of CGD (which affects only boys) is carried on the X chromosome ("X-linked"). The boys, who have one X and one Y chromosome, inherit their X- chromosomes from their mother. The mother, despite carrying one of the faulty genes on her X chromosome, is usually well (since she has another X chromosome without the faulty gene). Rarely some mothers may themselves have had a history of recurrent infections or had a history of mouth ulcers or recurrent light sensitive rash. If a mother carries the gene on one X chromosome, then half her sons on average will have CGD and half her daughters will be carriers. There is another, less common type of CGD, called autosomal recessive CGD, which can affect both boys and girls. In this type of CGD one affected gene is inherited from the father and one from the mother (neither parent will have a history themselves of having had recurrent or unusual infections typical of CGD).

Is there a test for CGD?

  • We can test for CGD using one of two special blood tests, (called the nitroblue tetrazolium test or the dihydrorhodamine test). Children with CGD will have abnormal neutrophils on either test.
  • These tests can also be used to check whether the mother is a carrier of the X-linked type of CGD.

Can CGD be diagnosed during pregnancy?

Antenatal diagnosis in pregnancy is possible, usually by doing a test called a chorionic villous biopsy to look for the gene. This test can only be done if the exact mutation (gene mistake) in the family has already been identified. An alternative test is to take a blood sample directly from the umbilical cord of the fetus and then perform a nitroblue tetrazolium or dihydrorhodamine test on the foetal blood.

What is the outlook for affected children?

With modern care, children affected by CGD are living into adult life. The severity of the disease varies, which means that some children have lots of infections and others have very few. Life expectancy in children who are less severely affected may be normal.

Can CGD be treated?

The antibiotic cotrimoxazole (Bactrim, Septrin) has improved things enormously for children with CGD. Taken every day, it prevents many of the bacterial infections patients with CGD are susceptible to, and is recommended in all patients with CGD. Some individuals with CGD may also be placed on daily anti-fungal therapy, such as itraconzole. Most children will be recommended to have, injections of interferon gamma on a long term basis to prevent infections. Interferon gamma is given three times a week by injection under the skin with a very small needle. Some individuals may complain of "flu-like" symptoms when starting the therapy, although most children tolerate the injections well.

Can it be cured?

The only possibility of cure is to perform a successful bone marrow transplant. Bone marrow transplant can be a dangerous procedure and may even be fatal, so it is not undertaken lightly and is not offered routinely. It will usually be discussed when the patient has a tissue matched sibling. Scientists have been interested in the possibility of using gene therapy (infecting CGD white cells with a virus carrying the normal gene for CGD) to cure CGD. However gene therapy does not currently result in a permanent cure. It is typically used as a "rescue" therapy, in those who are too sick to have bone marrow transplant, but in whom restoration of some neutrophil function may assist in fighting a serious infection, and improving the health of the individual, so that in the future bone marrow transplant may be feasible if a match is found.

Research programs are advancing rapidly, and it is hoped that in the future there may be more help or a cure for sufferers of the disease.

For more information

IDF Immune Deficiencies Foundation Australia
1800 465849
P O Box 198 Villawood, NSW, 2163
www.idaustralia.org

Remember

  • The antibiotic cotrimoxazole (Bactrim, Septrin) has improved lifestyle greatly for children with CGD.

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