« Understanding Primary Immunodeficiency (PI)

Types of PI

Primary immunodeficiency (PI) diseases are characterized in many different ways, including:

  • Low antibody levels
  • Defects in antibodies
  • Defects in the cells and proteins of the immune system (for example, T cells, B cells, neutrophils, or the complement system)

These defects make people susceptible to recurrent infections, and other complications that may require different therapies. The most common primary immunodeficiency types result in an inability to make a very important type of protein called antibodies or immunoglobulins, which help the body fight off infections from bacteria or viruses. In addition to increased susceptibility to infection, people with PI may also have autoimmune diseases in which the immune system attacks their own cells or tissues.

PI Type:

DiGeorge Syndrome

Definition of DiGeorge Syndrome

DiGeorge syndrome is a PI disease caused by abnormal formation of certain tissues during fetal development. The defect may affect the thymus gland and impair production of T lymphocytes.

Most people with DiGeorge syndrome have a genetic defect on chromosome 22. This leads to the abnormality in cells and tissue development, resulting in defects in the affected organs. Organ involvement and severity of organ involvement can vary between individuals.

Symptoms of DiGeorge Syndrome

Individuals with DiGeorge syndrome may have any or all of the following:

  • Facial appearance: Children may have an underdeveloped chin, eyes with heavy eyelids, ears that are rotated back and defective upper portions of their earlobes.
  • Parathyroid gland abnormalities: An underdeveloped parathyroid gland may cause hypoparathyroidism, leading to difficulty maintaining normal levels of calcium, called hypocalcemia. This may cause seizures or convulsions. The parathyroid defect often becomes less severe over time.
  • Heart defects: Most heart defects affect the aorta (blood vessel that takes oxygen-rich blood from the heart to the body), or the part of the heart from which the aorta develops. Some patients may have severe cardiac anomalies, while others may have none at all.
  • Thymus gland abnormalities: Underdevelopment or incomplete development of the thymus gland results in a smaller-than-normal sized thymus and decreased production of immune cells called T lymphocytes, or T cells. Not only do T cells destroy infected cells, they also help B lymphocytes (B cells) develop into plasma cells and produce immunoglobulins, or antibodies. This results in an increased risk of viral, fungal, and bacterial infections.
  • Autoimmunity: Patients with DiGeorge syndrome develop autoimmune disease at a higher rate than the general population. Autoimmune disease occurs when the immune system inappropriately attacks its own body.
  • Other clinical features: Individuals with DiGeorge syndrome may also have other developmental abnormalities, including cleft palate, poor function of the palate, delayed speech, and difficulty feeding and swallowing. Some people also have learning disabilities, behavioral problems, psychiatric disorders, and hyperactivity.
DiGeorge Syndrome Diagnosis DiGeorge Syndrome Diagnosis

Diagnosis of DiGeorge Syndrome

Traditionally, DiGeorge syndome was diagnosed when a person had the characteristics described above. However, people with DiGeorge syndrome differ not only in the organs and tissues affected, but also in terms of how severely a given organ or tissue is affected. This meant that many mild cases were missed when diagnosis relied on symptoms alone.

In recent years, diagnosis has been based on a genetic test that can detect the deleted section of chromosome 22, which is found in 90% of individuals with DiGeorge syndrome. The small proportion of patients without the genetic defect are diagnosed based on clinical features and by excluding a diagnosis of other syndromes.

Treating DiGeorge Syndrome

Only your doctor can determine which treatment is right for you and your specific health needs. Visit our Treating PI section to read about the types of PI treatment and download questions to ask your doctor.

For more information, please refer to the IDF Patient & Family Handbook for Primary Immunodeficiency Diseases (5th ed) by Blaese RM, Bonilla FA, Stiehm ER, Younger ME, eds.