Transient hypogammaglobulinaemia of infancy: low antibodies in young children

Immunoglobulins, also called antibodies, are proteins that help fight infection. GOSH explains that there are three main groups: IgG, IgA and IgM. "Hypogammaglobulinaemia" means low levels of these. GOSH describes THI as a condition where the immune system matures more slowly than usual, but eventually functions entirely normally, and says all types of immunoglobulin may be low, or one or two may be normal.

To understand it, it helps to know the normal pattern. GOSH explains that babies are born with immature immune systems and receive IgG from their mothers across the placenta in the last months of pregnancy. During the first six months this maternal IgG is gradually lost while the baby starts making its own, but because the baby makes IgG more slowly than it loses the mother's, total levels fall to a low at about six months, which is normal. Immunoglobulin levels then rise gradually until adult levels are reached at about 14 years. Babies born very early have less maternal IgG and may have an earlier and more marked dip.

In THI the baby is sometimes slow to start producing its own antibodies, so the low point is lower or lasts longer. GOSH says the cause is not known and that THI probably simply represents one end of the spectrum in how quickly the immune system develops.

GOSH says children with THI may have more frequent and prolonged infections than other children of similar ages, often throat and ear infections or non-specific viruses. A typical story is a child who is going to the doctor often and being given many courses of antibiotics, particularly in winter, and who sometimes becomes unwell again as soon as antibiotics stop.

GOSH emphasises that frequent infections in normal children are particularly common when they start to mix with others at nursery or school, and that lots of young children suffer frequent minor infections and have completely normal immune systems. Children with THI are occasionally at risk of serious infections such as pneumonia or meningitis, but GOSH says this is relatively unusual. The MSD Manual similarly says THI rarely leads to serious infections and is not thought to be a true immunodeficiency, although a few infants develop frequent sinus, lung or digestive tract infections, candidiasis or meningitis.

Speak to your GP or health visitor if your child seems to be having more frequent, longer or more severe infections than their peers, if infections come back as soon as antibiotics finish, or if they are not growing or gaining weight as expected. GOSH says that where there is concern about more frequent, prolonged or severe infections, the child may be referred to a paediatrician and possibly an immunologist.

Any baby or child who is very unwell, has a high temperature with a rash that does not fade under a glass, is breathing fast or with difficulty, is floppy or hard to wake, or has a stiff neck needs emergency help via 999 or A&E. These are general emergency signs, relevant to any child with a serious infection, not only to THI.

GOSH says a blood test is needed to measure immunoglobulin levels and probably to check for specific antibodies that should have been produced after vaccination against infections such as tetanus and Hib. It says it is unlikely that more complicated tests will be necessary. If the child has low levels of vaccination antibodies it may be necessary to give booster immunisations, followed by a repeat blood test, to check the child is properly protected and as a further test of the immune system.

Because antibody levels change as a child grows, as GOSH describes, results are interpreted by a paediatrician or immunologist. A low result in a single sample does not on its own mean there is a lasting problem.

The MSD Manual says that usually infants with the disorder produce normal amounts of antibodies in response to the vaccines they are given and to infectious organisms they are exposed to, which is part of how it is distinguished from more serious antibody deficiencies.

GOSH says there is no standard treatment for THI and that management aims at maintaining good day-to-day health and a normal life, including regular nursery or school attendance. Some children can be managed simply by treating infections quickly as they arise. If a child is getting very frequent infections, perhaps every four weeks, GOSH says they may be given a regular low dose of antibiotics, which can be very successful and can sometimes transform a child who is constantly unwell into a lively, happy one. Regular antibiotics can be continued for several years if necessary, though GOSH says this is unusual, and in some children they are only needed in the winter months.

In a very small group of children who have had or continue to have more serious infections, GOSH says replacement immunoglobulin may be considered and might be continued for several years. Ask the immunology team about vaccinations for your child.

GOSH says the problem gets better by school age in the vast majority of children, and that most children with recurrent infections and low immunoglobulins in infancy will not develop lifelong problems and will lead normal healthy lives. It notes that a small minority of children thought to have THI do not improve with time, with immunoglobulin levels remaining low or falling further, and in this very small number a long-term immune deficiency known as common variable immunodeficiency (CVID) develops. This is why follow-up and repeat testing are part of care.

GOSH also notes that there is a slightly increased risk for other children in the same family compared with the general population, but the overall risk is still very low.

On the NHS the route is usually GP or paediatrician, then a paediatric immunology clinic if needed. Private paediatric and immunology consultations exist and use the same tests, but the follow-up of a child with persistently low immunoglobulins is generally best coordinated with an NHS immunology service that sees these children regularly.