What is Transient Hypogammaglobulinemia of Infancy?
Transient hypogammaglobulinemia of infancy (THI) is a condition which affects the immune system of a baby. This condition occurs when there is a temporary decrease in the amount of immunoglobulin G (IgG) in a baby’s body, starting between the ages of 5 and 24 months. Immunoglobulin G (IgG) is a type of protein that our bodies use to fight off infections. In most cases, the level of IgG resumes to its normal range between ages 2 to 6 years.
It’s important to note that during pregnancy, a baby gets IgG from its mother, which is the only type of immunoglobulin that can cross the placenta. At birth, the baby’s IgG level usually equals its mother’s level. After birth, babies start to create their own IgG. Then, at around 6 months, their IgG levels typically increase to the expected amount while the mother’s IgG levels in their system start to decrease.
A normal decrease in IgG levels, known as physiologic hypogammaglobulinemia, takes place between 3 to 6 months when both the baby’s produced and the mother’s IgG levels are low. This temporary decrease is usually not a cause for concern. But in cases of THI, the baby’s IgG level remains considerably lower even past 6 months of age.
THI may cause recurring infections, but some babies may not show any symptoms. These babies can also have regular or slightly low levels of other types of immunoglobulins, such as IgA and IgM. Observing this mix of immunoglobulin levels helps doctors rule out a diagnosis of X-linked agammaglobulinemia, which is another immune system disorder. Nonetheless, other conditions impacting the immune system, such as common variable immunodeficiency, can’t be completely ruled out until the baby’s IgG levels return to normal as they grow older.
Usually, doctors confirm a diagnosis of THI when they look back at the baby’s medical history. Interestingly, male infants are affected two times more than female infants. Unfortunately, the cause and how often THI occurs are still unknown. When it comes to managing the condition, treating with antibiotics and replacing missing immunoglobulins in the babies who show symptoms are key aspects of the treatment plan.
What Causes Transient Hypogammaglobulinemia of Infancy?
The exact reason why some infants develop a condition called transient hypogammaglobulinemia is still not fully understood. Hypogammaglobulinemia is a medical term for having abnormally low levels of antibodies, which are substances that your body produces to fight off infections.
There are several theories that experts are considering. One theory suggests that the problem might be due to the ‘T cells’ in your body not properly prompting the ‘B cells’ to create antibodies. To explain better, ‘T cells’ and ‘B cells’ are types of cells in your immune system that work together to fight diseases – the ‘T cells’ signal the ‘B cells’ to produce these disease-fighting antibodies.
Another theory points to a scenario where the infant’s ability to make their own ‘IgG’ (a class of antibodies) could be impaired by the presence of the mother’s ‘IgG’ that the baby inherits at birth. Yet another theory suggests that the baby’s body may not be producing enough of certain substances known as ‘cytokines’ that are needed to regulate the immune response.
Finally, some scientists think genetic differences in families that have histories of immune system disorders might play a role.
Risk Factors and Frequency for Transient Hypogammaglobulinemia of Infancy
Transient hypogammaglobulinemia is a condition whose frequency is hard to pin down, as it differs from study to study. Some research even suggests that it might be the most common IgG deficiency found in children. This condition is seen all across the globe, but there’s a high chance that it doesn’t get diagnosed properly because the criteria for identifying it can vary.
- The condition tends to be more common in males.
- Over half of the patients are identified by the time they turn one.
- The rest are typically diagnosed after they turn five.
- It may take longer for people to recover if their initial IgM and IgA levels are low.
- Those patients who have been breastfed for a longer period tend to recover more quickly.
Signs and Symptoms of Transient Hypogammaglobulinemia of Infancy
Transient Hypogammaglobulinemia of Infancy is a condition during which a child may experience various symptoms primarily related to infections and allergies. Usual symptoms include respiratory tract infections and allergic reactions to food. More severe manifestations can range from urinary tract infections to gastroenteritis, and even invasive infections, depending on the specific type of infection present.
The conditions your child may encounter during this phase usually involve:
- Upper and lower respiratory tract infections
- Allergies including food allergies
- Urinary tract infections
- Gastroenteritis
- Invasive infections
Children suffering from this condition may also show the following symptoms:
- Sinus and lung infections
- Bloodstream infections
- Meningitis
- Middle ear infections
- Arthritis
- Sepsis, a serious infection
- Bronchiectasis, a chronic lung condition
- Frequent tonsillitis
- Pyodermitis, a skin infection
- Pus-producing eye infections
- Failure to gain weight or grow at a normal rate
- Aphthous stomatitis, also known as canker sores
- Diarrhea
- Continual weight loss
- Repetitive skin infections
- Autoimmune conditions
- Atopy, a tendency to develop allergies
- Sinus and lung infections
- Viral infections
- Neutropenia, low neutrophil count
- Persistent vomiting
- Fungal infections, such as candidiasis
However, not all babies show symptoms. In some cases, this condition might be diagnosed in babies who appear healthy but are being evaluated for immunological reasons or family history.
Testing for Transient Hypogammaglobulinemia of Infancy
If your doctor suspects that your infant may have transient hypogammaglobulinemia of infancy (THI), a condition that affects the immune system, they will carry out a series of tests. Here’s what you can usually expect:
Firstly, they’ll test the levels of different types of antibodies in your child’s blood. Antibodies are proteins produced by the immune system to fight infections. The main ones they’ll be testing for are called immunoglobulins (Ig) and these include IgG, IgM, IgA, as well as IgG1, IgG2, IgG3, and IgG4. In infants with THI, the IgG level in particular is usually significantly low. The levels of IgA and IgM could also be reduced, but this isn’t always the case.
Your doctor will also test your infant’s blood for certain types of antibodies produced in response to infections or vaccines. This includes those for conditions like measles, rubella, and varicella zoster (which causes chickenpox and shingles). Also, they’ll check for antibodies produced in response to immunizations including tetanus, diphtheria, and pneumococcal polysaccharide. Most of the time, infants with THI still respond well to these vaccines. If they don’t respond to a vaccine like the tetanus shot, then further testing may be done to check for other immune system disorders.
Additional tests done can include an examination of your child’s blood cells. This involves checking for the number of lymphocytes (a type of white blood cell), as well as different types of these cells known as T and B lymphocytes. The functioning of these cells is usually normal in infants with THI.
Furthermore, your child might also undergo some microbiological studies. These include various cultures of the blood, cerebrospinal fluid (fluid from the spine), stool, and sputum (saliva and mucus), among others, to look for any infections.
Finally, your doctor might order other tests based on your child’s condition and symptoms, such as DNA testing, a complete blood count, a chest X-ray, or a CT scan. These help to rule out other conditions that might be causing your child’s symptoms.
Treatment Options for Transient Hypogammaglobulinemia of Infancy
Transient hypogammaglobulinemia of infancy is a medical condition often treated in a conservative manner, meaning doctors will do their best to manage the symptoms without resorting to drastic measures.
If children start to show signs of infections, doctors might decide to use antibiotics as a preventative measure. For patients who suffer from repeated infections of the respiratory tract or severe life-threatening infections, despite taking antibiotics, doctors might suggest a course of treatment called intravenous immunoglobulin (IVIG). IVIG is a type of treatment where extra antibodies, which are proteins that fight infections, are injected into the patient’s vein to boost their immune system.
If the patient has allergic rhinitis, which is inflammation in the nose due to allergies, the doctor might prescribe nasal sprays that contain corticosteroids and antihistamines to manage the symptoms.
It’s also important for these children to stay up-to-date with their immunizations, including the heptavalent pneumococcal vaccine, a vaccine for a type of bacterial infection, which is normally given to children starting from the age of 2 months.
In terms of surgical treatments, if the child experiences frequent ear infections, the doctor might suggest putting in tympanostomy tubes, which are small tubes inserted into the eardrum to help drain fluid and prevent infections. For chronic sinusitis, which is a long-term inflammation of the sinuses, a type of minimally invasive surgery called Functional Endoscopic Sinus Surgery (FESS) might be considered.
What else can Transient Hypogammaglobulinemia of Infancy be?
When a baby has temporary low levels of certain key immune proteins (a condition known as “transient hypogammaglobulinemia of infancy”), doctors often need to rule out other medical conditions that could cause similar symptoms. These may include:
- X-linked (Bruton) agammaglobulinemia: Boys with this condition often have recurrent bacterial infections. Genes related to the body’s immune system, specifically a mutation in the Bruton tyrosine kinase (BTK) gene, may be detected through genetic studies.
- Common variable immunodeficiency: This condition is characterized by recurrent bacterial infections that usually occur later in life, generally between the second to fourth decades. The diagnosis is confirmed once all other possible causes of immune system issues have been ruled out.
What to expect with Transient Hypogammaglobulinemia of Infancy
Transient hypogammaglobulinemia of infancy, or THI, is a condition that affects the immune system of infants. The future health outcomes of those with THI largely hinge on how severe the condition is. Fortunately, for those showing symptoms or experiencing only a mild form of the disease, the outlook is generally positive and doesn’t lead to major health issues.
However, individuals presenting severe forms of the disease may face challenges such as opportunistic infections, or atopy and autoimmunity. These are conditions in which the immune system is either weakened and more likely to get infections (opportunistic infections), or becomes overactive and attacks the body’s own cells (atopy and autoimmunity).
In some cases, the severity of the disease may somewhat resemble another condition called X-linked agammaglobulinemia. These patients will require lifelong treatment with antimicrobials (drugs that kill microorganisms or stop their growth) and IVIG, or Intravenous Immunoglobulin (a treatment that provides the body with antibodies it needs to protect against diseases).
That said, THI is defined as a condition that should completely resolve eventually. So, even in severe cases, the disease does not persist forever.
Possible Complications When Diagnosed with Transient Hypogammaglobulinemia of Infancy
Complications associated with a condition known as “transient hypogammaglobulinemia of infancy” include:
- Fungal infections, such as oral candidiasis
- Bacteremia, which is the presence of bacteria in the blood
- Premature death
- Anaphylaxis, a severe allergic reaction
- Chronic diarrhea
- Neutropenia, a condition of low neutrophil count
- Food allergies
Preventing Transient Hypogammaglobulinemia of Infancy
If your child is diagnosed with a condition called transient hypogammaglobulinemia of infancy, it’s crucial to understand the risk of infections associated with this condition. Transient hypogammaglobulinemia of infancy affects the immune system, which makes it harder for the body to fight off infections.
To help manage this condition, the consistent use of prescribed medications, such as antibiotics, immunoglobulins (proteins used by the immune system to ward off bacteria and viruses), and antihistamines (medications to treat allergic reactions), is essential. Regular use of these medicines can help to lessen complications and support your child’s health.
