Hypogammaglobulinemia describes low levels of immunoglobulins in your body. Immunoglobulins are antibodies that fight germs like viruses and bacteria that can make you sick. Having low levels may increase your risk of infections and other diseases. Antibiotics, immunoglobulin replacement therapy and stem cell transplant are potential treatments.


What is hypogammaglobulinemia?

Hypogammaglobulinemia means having low levels of antibodies called immunoglobulins in your immune system. Your immune system protects you from germs like viruses and bacteria that can make you sick. It includes immune cells, like B-cells, that defend you from germs and fight disease. When a germ enters your body, B-cells make immunoglobulins to destroy it.

You may learn that you have hypogammaglobulinemia when you get results from a blood test.

The word provides clues about what’s involved:

  • Hypo: Below normal.
  • Gamma globulins: The most common type of immunoglobulin.
  • Emia: In your blood.

Having low levels of immunoglobulins weakens your body’s defenses against invaders. It increases your risk of infections and other illnesses.

Types of hypogammaglobulinemia

Hypogammaglobulinemia can affect both children and adults. There are two main types:

  • Primary (congenital) hypogammaglobulinemia: Several rare genetic disorders called primary immunodeficiency disease (PIDD) cause low immunoglobulin. With PIDD, you’re born with a mutation, or error, in the genetic material that tells your immune system how to work. These mutations often run in biological families.
  • Secondary (acquired) hypogammaglobulinemia: Medical conditions and medications can also cause low immunoglobulin levels. The majority of people with hypogammaglobulinemia get it because of a condition or medication side effect.

How rare is hypogammaglobulinemia?

Hypogammaglobulinemia is the most common PIDD. Still, PIDDs are uncommon. Approximately 500,000 people in the U.S. are living with PIDDs.


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Symptoms and Causes

What are the symptoms?

The most common sign of hypogammaglobulinemia in children and adults is long-lasting or frequent infections. Symptoms depend on the type of infection. Common infections associated with hypogammaglobulinemia (and commonly associated symptoms) include:

  • Ear infections (ear pain, scarred eardrum, fever).
  • Sinus infections (runny or stuffy nose, fatigue, fever).
  • Bronchitis (persistent cough, shortness of breath, fever).
  • Pneumonia (congestion or chest pain, shortness of breath, fever).
  • Stomach flu (diarrhea, nausea, vomiting, fever).
  • Meningitis (neck stiffness, headache, fever).
  • Skin infections (rash, swelling, itching, fever).

Symptoms also depend on the condition that’s causing low immunoglobulin levels. For example, some types of PIDD may make a child more likely to have allergies. Other types can slow growth and development in children.

What causes hypogammaglobulinemia?

Your immune system may not make enough immunoglobulins, or something destroys them. Causes differ depending on whether you have primary or secondary hypogammaglobulinemia.

Primary hypogammaglobulinemia

Some of the PIDDs most commonly associated with hypogammaglobulinemia include:

  • Common variable immunodeficiency (CVID): Various gene mutations prevent your body from making enough immunoglobulin. CVID is the most common cause of primary hypogammaglobulinemia in adults.
  • X-linked agammaglobulinemia (XLA): A mutation on the X chromosome prevents your body from making enough B-cells or immunoglobulins. XLA primarily affects babies assigned male at birth (as they only have one X chromosome). XLA is a common cause of hypogammaglobulinemia in children.
  • Transient hypogammaglobulinemia of infancy (THI): Immunoglobulin levels start falling at around 3 months old. Infants with THI may develop infections, but often they don’t show symptoms. THI usually resolves on its own before age 3.
  • Selective IgA deficiency: Your body doesn’t produce enough of a specific type of immunoglobulin, immunoglobulin A.
  • Hyper-IgM syndromes: Your body produces normal or increased levels of some types of immunoglobulin but not enough of others.

Other PIDDs that cause primary hypogammaglobulinemia include:

  • Ataxia-telangiectasia.
  • Autosomal recessive agammaglobulinemia (ARA).
  • Good syndrome (GS).
  • Isolated non-IgG immunoglobulin deficiencies.
  • Severe combined immunodeficiency (SCID).
  • Specific antibody deficiency (SAD).
  • Wiskott-Aldrich syndrome (WAS).

Secondary hypogammaglobulinemia

Acquired causes of hypogammaglobulinemia include:


What are the complications of hypogammaglobulinemia?

Without treatment, hypogammaglobulinemia can cause severe infections with potentially life-threatening complications. One of the most common complications is bronchiectasis. This condition involves irreversible lung damage. It's common among people with frequent upper respiratory infections.

Hypogammaglobulinemia can also increase your risk of developing:

Diagnosis and Tests

How is hypogammaglobulinemia diagnosed?

Healthcare providers use blood tests to measure your immunoglobulin levels. If your levels are below what’s considered normal, you have hypogammaglobulinemia. Your provider will classify your hypogammaglobulinemia as mild, moderate or severe.

To determine what’s causing your low levels, they’ll consider:

  • Your symptoms, including whether you get frequent infections.
  • Your family medical history, including a family history of PIDD.
  • Medications you’re taking, especially drugs with hypogammaglobulinemia as a potential side effect.

You may need more tests, including:


Management and Treatment

How is hypogammaglobulinemia treated?

Treatment depends on what’s causing your hypogammaglobulinemia and how serious it is. You may need to see a doctor who specializes in immune diseases (immunologist) for treatment. With secondary causes, healthcare providers usually treat the underlying condition. They may switch your medicine if it’s causing low immunoglobulin levels as a side effect. Primary hypogammaglobulinemia often requires lifelong monitoring to prevent severe infections. Treatment options include:

  • Watchful waiting: Your healthcare provider may monitor your condition if your low levels don’t pose health risks. You may not need treatment for conditions that improve on their own, like transient hypogammaglobulinemia of infancy.
  • Antibiotics: You may need antibiotics to treat or prevent a bacterial infection.
  • Immunoglobulin (IgG) replacement therapy: You may need immunoglobulin from a donor if you have severely low levels. You’ll receive immunoglobulin through a vein (IV) or a shot in a muscle (subcutaneous). People with PIDD who need this treatment often need it throughout their lives.
  • Stem cell transplant: You may need stem cells from a donor if your body can’t make healthy immune cells. Stem cells eventually mature into healthy blood cells, including B-cells.


Can hypogammaglobulinemia be prevented?

The conditions that cause hypogammaglobulinemia aren’t preventable. Still, your healthcare provider can recommend treatments to prevent complications.

Outlook / Prognosis

Is hypogammaglobulinemia serious?

Hypogammaglobulinemia can be serious depending on what’s causing it and how low your levels are. Immunoglobulins fight harmful pathogens like viruses, bacteria, parasites and fungi. Without these fighters to protect you, you’re at risk of developing frequent and serious infections. Untreated severe infections can cause long-term tissue damage and even be fatal.

What happens if hypogammaglobulinemia goes untreated?

It’s essential to have a healthcare provider diagnose what’s causing hypogammaglobulinemia. Early treatment can give you a better chance of being healthy and avoiding complications years from now. If you have a condition that puts you at risk of hypogammaglobulinemia, your healthcare provider will monitor your levels. They can recommend a care plan to prevent serious infections.

Living With

How do I take care of myself?

Follow your healthcare provider’s guidance on preventing infections. Tips include:

  • Frequent handwashing.
  • Masking when appropriate to prevent the spread of airborne germs.
  • Avoiding people who are sick or crowds where airborne germs can easily spread.
  • Staying up-to-date on all vaccines. (Follow your healthcare provider’s guidance on whether it’s safe to receive live vaccines.)

What questions should I ask my healthcare provider?

  • What’s causing my low immunoglobulin levels?
  • What tests will I need to diagnose/monitor my condition?
  • What treatments do you recommend?
  • What are potential treatment side effects?
  • What lifestyle changes do you recommend to avoid infections?
  • What symptoms require an in-office visit? A visit to the ER?

A note from Cleveland Clinic

Learning you have low levels of immunoglobulins may make you feel defenseless or vulnerable. These fighters protect you from infection. So, what will happen if they’re not at full strength?

You may have lots of questions. But talking to your healthcare provider is the first step toward learning more about your condition, what’s causing it and how treatments can help. Work with your provider to manage this condition and get the care you need.

Medically Reviewed

Last reviewed on 08/14/2023.

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