Hyper Igm Syndrome

Overview

Hyper IgM syndrome is a rare condition that a person is born with. It affects the immune system — the body's defence against infection. In this condition, the body makes immune cells called B cells, but these cells cannot 'switch' to make the full range of antibodies (protective proteins that fight germs). Instead, they keep making mostly one type, called IgM, while other important types — IgG, IgA and IgE — stay low. Because those other antibodies are missing, people with the condition catch infections more easily and more often than other people.

It is very rare. Only a small number of families around the world are affected, and many general doctors will never see a case in their whole career.

Most people are diagnosed in early childhood, usually in the first year or two of life. The most common type affects almost only boys, because it is linked to the X chromosome. The rarer types affect boys and girls equally and may be diagnosed later, sometimes in adulthood.

Symptoms

Common symptoms

• Infections that keep coming back, or that are more severe than usual — especially chest, ear, sinus and throat infections.
• Pneumonia that is hard to clear, or that returns.
• Long-lasting or repeated diarrhoea, sometimes with weight loss.
• Mouth sores, or thrush (white patches in the mouth).
• Skin infections or boils.
• Swollen lymph nodes (the 'glands' in the neck, armpits or groin) that stay enlarged.
• Feeling very tired, or poor growth in children.
• Autoimmune problems in some people — where the immune system mistakenly attacks the body's own cells.

Symptoms in children

• Infections that start around 6 months old, once the antibodies passed from the mother during pregnancy have faded.
• Slow weight gain or poor growth (sometimes called failure to thrive).
• Ongoing diarrhoea or feeding difficulties.
• Frequent ear infections, which can affect hearing and speech.
• In some babies, a serious lung infection called Pneumocystis pneumonia is the first sign — this needs urgent medical care.

Symptoms in older adults

• Most people with the common forms are diagnosed in childhood, so being diagnosed for the first time in later life is uncommon.
• Adults diagnosed late often describe many years of repeated sinus or chest infections.
• Some adults develop lasting lung effects, such as scarring or bronchiectasis (damaged, widened airways that collect mucus).
• Liver problems can develop, sometimes triggered by a gut infection that reaches the liver.
• Autoimmune conditions and some blood problems are seen more often in adults living with the condition.

Causes

Main causes

• It is caused by changes (variants) in genes that tell immune cells how to switch from making IgM to making other antibody types.
• The most common form involves a gene on the X chromosome, often called CD40 ligand deficiency.
• Other forms are passed on when both parents carry a copy of a changed gene. This pattern is called autosomal recessive inheritance.
• In some people the exact genetic cause has not yet been found.

Risk factors

• Having a family member with this condition, or with a similar immune problem.
• Being male — the most common form is X-linked.
• Parents who are closely related have a higher chance of passing on the recessive forms.
• The condition is not caused by diet, lifestyle, stress, hygiene or where you live.

When to see a doctor

See a doctor urgently if:

• A temperature of 38°C (100.4°F) or higher, or any fever in a baby under 3 months.
• Breathing difficulty, fast breathing, or chest pain.
• Diarrhoea lasting more than a few days, or signs of dehydration.
• A skin infection that is spreading, hot or very painful.

Book a routine appointment if:

• You or your child keep getting infections — for example, several ear or chest infections in a year.
• Infections need antibiotics more often than usual, or take a long time to clear.
• Poor growth, ongoing tiredness, or weight loss without a clear reason.
• You have a family history of immune problems and want advice, including before starting a family.

Diagnosis

A GP who suspects an immune problem will usually arrange blood tests and refer you or your child to an immunologist — a doctor who specialises in the immune system. The diagnosis is made by measuring the different antibody types in the blood and, in most cases, by confirming a gene change with a genetic test.

Tests that may be done

• Blood tests to measure antibody levels (IgM, IgG, IgA and IgE).
• A full blood count to check the white cells, including looking for low levels of cells called neutrophils.
• Tests to see how well the immune system responds to vaccines.
• Genetic testing, using a blood or saliva sample, to look for the changed gene.
• Tests to look for specific infections, or to check the lungs or liver if there are symptoms.
• Sometimes tests on family members to see whether they carry the same gene change.

What to expect at your appointment

Waiting for results can be an anxious time. Blood test results usually come back within a few weeks, and genetic tests can take longer. You will normally be seen by a specialist team who will explain what the results mean. If the diagnosis is confirmed, they will go through a care plan with you. Nothing is decided without your agreement, and you can ask as many questions as you need.

Treatment

There is no simple cure, but treatment works well. The main aims are to replace the antibodies the body cannot make and to treat infections quickly. Most people are looked after by a specialist immunology team, with regular check-ups.

Self-care at home

• Wash your hands often, and teach children to do the same.
• Keep up with routine appointments — regular check-ups catch problems early.
• Ask your team before any vaccination, especially live vaccines.
• Avoid unpasteurised dairy, and, if your team advises it, drink boiled or filtered water to lower the risk of a gut infection that can harm the liver.
• Stay away from people with chickenpox, measles or shingles if you have not had them before — and tell your team straight away if you think you have been exposed.
• Keep a simple diary of infections and temperatures to share at appointments.
• Never stop or change a treatment without speaking to your team first.

Medical treatments

Specialists usually replace the missing antibodies with immunoglobulin therapy. This means donated antibodies given either through a drip into a vein at a clinic, or as regular injections under the skin at home after training. It is not a medicine in the usual sense — it is a blood product that gives the body the antibodies it cannot make. Antibiotics are used to treat infections, and some people take a low-dose antibiotic regularly to help prevent them. Other treatments can help with autoimmune problems or low white cell counts. In some severe cases, a stem cell (bone marrow) transplant may be offered as a possible long-term cure; the specialist team will explain the risks and benefits in detail.

When is surgery considered?

Surgery is not a treatment for the condition itself. Some people need operations for complications — for example, sinus surgery for long-standing sinus problems, or a procedure to check the liver or take a sample of a lymph node. A stem cell transplant is a specialised procedure offered in selected cases only. Your specialist team would explain any procedure carefully beforehand.

Living with this condition

Day-to-day life is mostly about routine. Many people learn to give themselves immunoglobulin at home, which fits around school and work. Your specialist team will usually give you a written plan covering what to do if you get a fever, who to call, and which antibiotics to start — follow that plan and keep it with you or on your phone.

Lifestyle tips

• Carry a card or use an app that says you have an immune condition, in case you need emergency care.
• Avoid smoking and smoky rooms to protect your lungs.
• Keep up with school, work and activities — exercise and a normal social life are encouraged.
• Ask your team which vaccines are safe for you and for the people you live with.
• Plan travel with your team — they can provide letters and advice about food and water safety.

Diet and exercise

There is no special diet for this condition. A balanced, varied diet and plenty of fluids help you recover from infections. Gentle, regular exercise — walking, swimming, cycling — helps keep your lungs and muscles strong. Build up slowly after an infection, and check with your team before starting anything strenuous if you have lung or heart problems.

Mental health and emotional wellbeing

Living with a rare, lifelong condition can be hard — for the person and for parents, brothers and sisters. It is normal to feel anxious, tired of appointments, or isolated, especially around diagnosis or during a run of infections. Talking about it helps. Tell your specialist team how you are feeling; they can arrange psychology or counselling support. If you ever feel you cannot cope, or have thoughts of harming yourself, contact your local crisis line or emergency services straight away. You deserve help quickly and you will not be judged.

Prevention

No. The condition is written into a person's genes, so it cannot be prevented, and nothing a parent did or did not do causes it. What can be prevented is the harm it causes. Early diagnosis, antibody replacement therapy, prompt treatment of infections, and avoiding certain infections all greatly reduce the risk of complications.

Vaccines

Live vaccines — such as some measles, mumps and rubella, chickenpox, and oral polio vaccines — are usually avoided in people with this condition, because they can cause infection. Inactivated (killed) vaccines are generally safer, though they may not work as well. Always check with your immunology team before any vaccine, and ask which vaccines are recommended for the people you live with.

Screening programmes

There is no routine screening test for the general population. If a gene change is found in your family, genetic counselling and testing of relatives — including newborn babies — is usually offered, so that treatment can start early if needed. Ask your specialist team about family screening.

Complications

If left untreated

• Repeated, severe infections of the chest, ears, sinuses and gut.
• Permanent lung damage, such as bronchiectasis (scarred, widened airways).
• Liver disease, which can be serious, often triggered by a gut infection.
• Low neutrophil counts, which make infections even more likely.
• Autoimmune problems, where the body attacks its own blood cells or tissues.
• Poor growth and development in children.
• A higher than average risk of certain cancers, especially of the immune system. This is uncommon and is watched for at check-ups.

Long-term outlook

The outlook today is far better than it used to be. With early diagnosis, regular antibody replacement and prompt treatment of infections, many children grow up to live full, active adult lives — going to school, working and having families of their own. Some people are cured with a stem cell transplant. Living with a long-term condition does take effort, but you will have a specialist team alongside you, and there is a lot of reason for hope.

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