What is Primary Immunodeficiency?
Primary Immunodeficiency (PI), also known as Inborn Errors of Immunity, are a group of more than 550 genetic disorders of the immune system that are chronic, serious, and sometimes life-threatening. PIs occur when genetic mutations cause one or more parts of the immune system to not work properly. A weakened immune system increases the risk of frequent and severe infections, and potential organ damage. PI affects up to 83 million people worldwide.
How is PI Diagnosed and Treated?
Early diagnosis and proper treatment significantly improve the quality of life for patients living with PI.
Certain types of PI can be detected and diagnosed through newborn screening (at birth) or genetic testing, but in all cases, your medical history and symptoms will be assessed to help determine what type of testing may be necessary to confirm a diagnosis.
There are many different treatment options available depending on your specific type of PI. Some examples of treatment include immunoglobulin (Ig) replacement therapy, gene therapy, and bone marrow transplant. Your physician will determine the best treatment option for your specific case.
PI Definitions
There are more than 550 types of Primary Immunodeficiency. To learn about a specific type, click through the list below.
- ADA Deficiency
Adenosine Deaminase (ADA) Deficiency is an autosomal recessive condition that causes Severe Combined Immune Deficiency (SCID). ADA Deficiency is characterized by frequent and persistent severe infections. This condition is fatal if those affected do not receive treatment through hematopoietic stem cell transplantation (HSCT). Gene therapy and enzyme replacement therapy are additional treatment options.
Learn more about ADA Deficiency
- APDS - Activated P13K Delta Syndrome
APDS, or Activated P13K Delta Syndrome, is a rare primary immunodeficiency that affects 1-2 people in a million. APDS occurs when there is an abnormal change in either one of two specific genes, the PIK3CD gene or the PIK3R1 gene. The genes follow an autosomal dominant mode of inheritance and are involved in making parts of a protein that help in the growth and division of white blood cells, particularly the B-cell and T-cell lymphocytes. The changes in these genes lead to the creation of an enzyme (PI3KD) that is more active than normal, causing abnormal development and control of B- and T-lymphocytes; as a result, their ability to recognize, prevent, or fight off bacterial and viral infections is reduced. Symptoms of APDS start in childhood, and patients are vulnerable to repeat infections and autoimmune/inflammatory symptoms such as lymphoproliferation, splenomegaly, and even lymphoma. Cases of short syndrome and neurological cognitive deficit has also been observed. Patients are often misdiagnosed with other immunodeficiencies or autoimmune disorders. Diagnosis is made by a genetic test, and regular health checkups are required. Clinical trials are underway to find a treatment for APDS.
To learn more about APDS and steps to diagnosing the condition, including information about a recently launched sponsored genetic testing program, please visit www.allaboutapds.com
- Artemis Deficiency
Artemis Deficiency causes one of the most aggressive forms of Severe Combined Immune Deficiency (SCID), characterized by absence of B cells and T cells. This form of SCID is caused by mutations in the Artemis gene inherited in an autosomal recessive pattern. Infants with Artemis Deficiency experience severe, life-threatening infections, and oral/genital ulcers. This condition is fatal in the first year of life if not treated with bone marrow transplantation.
Learn more about Artemis Deficiency:
- Ataxia Telangiectasia
Ataxia Telangiectasia is a disorder inherited in an autosomal recessive pattern that affects the immune system and nervous system. It is caused by a mutation in the ATM gene. Symptoms usually present before the age of 5 and include difficulty with movement, coordination, and balance. Children with Ataxia Telangiectasia also have weakened immune systems and are at increased risk of developing cancers such as Leukemia and Lymphoma. Approximately 1 in 40,000 to 1 in 100,000 are affected by Ataxia Telangiectasia globally.
Learn more about Ataxia Telangiectasia:
- Autoimmune Lymphoproliferative Syndrome (ALPS)
Autoimmune Lymphoproliferative Syndrome (ALPS) is a genetic disorder most commonly caused by a mutation in the FAS gene. ALPS is characterized by the overproduction of lymphocytes, causing enlargement of the lymph nodes, spleen, and liver. Symptoms may include arthritis, skin rashes, and neurologic damage, as well as increased susceptibility to autoimmune disorders and cancers. ALPS- FAS is generally passed on in an autosomal dominant pattern.
Learn more about ALPS Deficiencies:
- Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED)
Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a genetic condition caused by mutations in the AIRE gene inherited in autosomal recessive patterns. APECED is characterized by chronic candida infections, autoimmune hypoparathyroidism, and Addison’s Disease. It is mostly prevalent in Finnish, Iranian Jewish, Norwegian, and Sardinian populations.
Learn more about APECED:
- C1 Inhibitor Deficiency
C1 Inhibitor Deficiency is an autosomal dominant Primary Immunodeficiency that causes inflammation in the respiratory and gastrointestinal tracts. People with C1 Inhibitor Deficiency may show signs and symptoms early in life, and usually have a family history. Clinically, C1 Inhibitor Deficiency is characterized by angioedema, accumulation of fluid in the larynx, and gastrointestinal tract inflammation. There are over 100 gene mutations that cause this deficiency. Approximately 1 in 50,000 people are affected worldwide.
Learn more about C1 Inhibitor Deficiency:
- Cartilage Hair Hypoplasia
Cartilage Hair Hypoplasia is a condition caused by mutations in the RMRP gene, which is inherited in an autosomal recessive pattern. Mutations in the RMRP gene cause an overproduction of RNA, which interferes with normal cell function. Characteristics of Cartilage Hair Hypoplasia include abnormal skeletal growth, short stature, fine and thinning hair, as well as recurring infections and gastrointestinal dysfunction.
Learn more about Cartilage Hair Hypoplasia:
- Chediak-Higashi Syndrome
Chediak-Higashi Syndrome is a genetic condition caused by a mutation in the LYST gene, inherited in an autosomal recessive pattern. This condition is characterized by an abnormal function of proteins that control production of lysosomes, leading to interference of normal cell function and poor immune system function. Chediak-Higashi Syndrome is characterized by frequent infections, oculocutaneous albinism (abnormal pigmentation), vision problems, frequent bruising, and abnormal bleeding.
Learn more about Chediak-Higashi Syndrome:
- Chronic Granulomatous Disease
Chronic Granulomatous Disease is a Primary Immunodeficiency in which affected individuals have recurrent viral and bacterial infections, most commonly in the lungs. Individuals with Chronic Granulomatous Disease often have inflammation in tissues within the gastrointestinal and genitourinary tracts that can be damaging. Chronic Granulomatous Disease is caused by genetic mutations inherited in X-linked recessive and autosomal recessive patterns. Symptoms may include abscesses, difficult to clear skin infections, bone and joint infections, persistent diarrhea, and frequent pneumonias.
Learn more about Chronic Granulomatous Disease:
- Chronic Mucocutaneous Candidiasis
Chronic Mucocutaneous Candidiasis is caused by mutations in genes inherited in both autosomal recessive and dominant patterns. Mutations in the AIRE gene (autoimmune regulator) cause autosomal recessive inherited CMC, while mutations in STAT1 underlie autosomal dominant inherited CMC. Characteristics include candida infections of the skin, mucous membranes, and nails.
Learn more about Chronic Mucocutaneous Candidiasis:
- http://www.ncbi.nlm.nih.gov/pubmed/21714643
- http://www.ncbi.nlm.nih.gov/pubmed/21727188
- http://emedicine.medscape.com/article/1091928-overview
Clinical Trial Opportunity for Patients with Chronic Mucocutaneous Candidiasis
Chronic Mucocutaneous Candidiasis often results from an underlying immune deficiency that leads to abnormalities in a person’s control of fungal infections such as candida. Investigators at NIAID are seeking people with chronic mucocutaneous candidiasis (oropharyngeal, esophageal or vulvovaginal candidiasis) that are refractory or intolerant to standard non-intravenous therapies to participate in a clinical research trial. For additional information please contact Dr. Alexandra Freeman (freemaal@mail.nih.gov) or see https://clinicaltrials.gov/ct2/show/NCT02629419.
- Comel-Netherton Syndrome
Comel-Netherton Syndrome is a disorder caused by mutations in the SPINK5 gene, which is inherited in an autosomal recessive pattern. Comel-Netherton Syndrome is characterized by abnormal skin (eczema, itching, scaly edges, inability to protect from the heat and cold), hair (rigid, bamboo-like shafts), and immune system (allergies, short stature, high serum levels of IgE).
Learn more about Comel-Netherton Syndrome:
- Common Variable Immunodeficiency
Common Variable Immunodeficiency is characterized by frequent bacterial infections, commonly of the upper and lower respiratory tracts, low levels of immunoglobulin, and B-cell dysfunction. Specifically, people with Common Variable Immunodeficiency (CVID) have increased occurrences of pneumonias, sinusitis, influenza, and gastrointestinal inflammation. CVID is diagnosed by measuring for low serum IgG, and sometimes reduced concentration in IgA and IgM. Some people with CVID may also have autoimmune manifestations. Signs and symptoms may develop in childhood, though many are diagnosed in adulthood.
Learn more about Common Variable Immunodeficiency:
- Complement Deficiencies
Complement Deficiencies are caused by genetic defects of the innate immune system. People with Complement Deficiencies are susceptible to recurrent bacterial infections and sepsis. Autoimmune disorders may also manifest, such as Systemic Lupus Erythematosus.
Learn more about Complement Deficiencies:
- DiGeorge Syndrome
DiGeorge Syndrome is caused by a deletion of genes on chromosome 22. Symptoms of DiGeorge Syndrome may include frequent infections, heart complications, thyroid dysfunction, poor muscle tone, failure to thrive, delayed development, and cleft palate. Treatments are available for complications that may arise from DiGeorge Syndrome.
Learn more about DiGeorge Syndrome:
- EDA-ID, X-Linked Deficiency
Anhidrotic Ectodermal Dysplasia with Immune Deficiency (EDA-ID) is a group of conditions characterized by lack of immunoglobulins and abnormal development of the skin, teeth, hair, and sweat glands. EDA-ID, X-Linked is caused by mutations in the IKBKG gene, which is inherited in a recessive pattern, affecting mostly males. Symptoms include frequent pneumonias, sinusitis, inflammatory bowel disease, skin abnormalities (dry, wrinkled appearance), and teeth abnormalities (small and pointed in appearance). This condition is associated with NEMO (NF-kappa B essential modulator) mutations.
Learn more about EDA-ID X-linked Deficiency:
- ELANE-Related Deficiencies
ELANE-Related Deficiencies cause congenital neutropenia, which is characterized by frequent fevers, inflammation, ulcers, sinusitis, pharyngitis, deep abscesses in organs, pneumonias, and diarrhea. Congenital neutropenia is often diagnosed in the first year of life. Mutations in the ELANE gene are inherited in an autosomal dominant pattern.
Learn more about ELANE Deficiencies:
- Familial Hemophagocytic Lymphohistiocytosis
Familial Hemophagocytic Lymphohistiocytosis (FHL) is a condition caused by several genetic mutations inherited in autosomal recessive patterns. FHL is characterized by overproduction of T cells, B cells, Natural Killer cells, and macrophages, causing fever, spleen and liver damage, abnormal bleeding, and frequent bruising.
Learn more about FHL and related Perforin Deficiencies:
- Familial Mediterranean Fever
Familial Hemophagocytic Lymphohistiocytosis (FHL) is a condition caused by several genetic mutations inherited in autosomal recessive patterns. FHL is characterized by overproduction of T cells, B cells, Natural Killer cells, and macrophages, causing fever, spleen and liver damage, abnormal bleeding, and frequent bruising.
Learn more about FHL and related Perforin Deficiencies:
- Griscelli Syndrome
Griscelli Syndrome is a disorder caused by mutations in the MYO5A, RAB27A, and MLPH genes, which are inherited in an autosomal recessive pattern. Type 2 (RAB27A) is the most frequent type of Griscelli Syndrome, characterized by recurrent infections, organ and tissue damage, and abnormalities in pigmentation of hair and skin.
Learn more about Griscelli Syndrome:
- Hermansky-Pudlak Syndrome
Hermansky-Pudlak Syndrome is caused by mutations in several genes, inherited in an autosomal recessive pattern. Hermansky-Pudlak Syndrome is characterized by oculocutaneous albinism, causing abnormal pigmentation of the eyes, skin, and hair. Symptoms may also include vision problems, sensitivity to light, frequent bruising and abnormal bleeding, and issues with breathing caused by pulmonary fibrosis.
Learn more about Hermansky-Pudlak Syndrome:
- Hyper IgD Syndrome
Hyper IgD Syndrome is a condition caused by mutations in the MVK gene and is inherited in an autosomal recessive pattern. Hyper IgD Syndrome is characterized by periodic fevers, skin rashes, abdominal and joint pain. Episodes of periodic fever usually occur in infancy.
Learn more about Hyper IgD Syndrome:
- Hyper IgE Syndrome, Autosomal Dominant
Hyper IgE Syndrome, also known as Job Syndrome, is a deficiency that causes overproduction of serum IgE. Autosomal Dominant Hyper IgE Syndrome is caused by a mutation in STAT3, leading to abnormalities in skin (rashes, boils), the skeleton (scoliosis, fractures, hyperextension of joints), and of the vasculature (aneurysms).
Learn more about Autosomal Dominant Hyper IgE Syndrome:
- Hyper IgE Syndrome, Autosomal Recessive
Hyper IgE Syndrome is a deficiency that causes overproduction of serum IgE. Autosomal Recessive Hyper IgE Syndrome is caused by mutations in the DOCK8 gene, leading to abnormalities in skin (rashes, boils), frequent pneumonias, and higher susceptibility to viral infections such as Herpes Simplex Virus.
Learn more about Hyper IgE Syndrome, Autosomal Recessive:
- Hyper IgM Syndrome
Hyper IgM Syndrome causes abnormal levels of proteins called antibodies or immunoglobulin. It is usually inherited as an X-Linked recessive trait, predominantly affecting males. X-Linked Hyper IgM is caused by mutations in the gene that controls production of the protein CD40 ligand. There are different types of antibodies with different functions. In this case, patients have abnormally low levels of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE). Low levels of these antibodies make it difficult to fight off infections. Symptoms present themselves in infancy and early childhood. Patients often suffer from pneumonia, sinusitis, and otitis. Growth and weight gain are also affected. This syndrome occurs in about 2 in 1 million newborn boys.
Learn more about X-Linked Hyper IgM Syndrome:
- Hypogammaglobulinemia
Hypogammaglobulinemia is characterized by recurrent infections normally prevented by appropriate antibody response. Infections of the upper and lower respiratory tract (such as pneumonia, sinusitis, and bronchitis), gastrointestinal tract, skin, and joints occur more frequently for people with Hypogammaglobulinemia. Quantitative measurements of serum immunoglobulins can assist in diagnosis of Hypogammaglobulinemia. Treatment may include IgG replacement therapy.
Learn more about Hypogammaglobulinemia:
- IgA with IgG Subclass Deficiency
IgG Subclass Deficiencies affect the production of antibodies. Many patients with IgA Deficiency are asymptomatic. However, respiratory, ear, and sinus infections may occur more frequently in patients who also have IgG Subclass Deficiencies. Onset of infections may occur later in life. Males and females can both be affected.
Learn more about IgA with IgG Subclass Deficiencies:
- IgG Subclass Deficiency
There are a total of 5 subclasses of immunoglobulins (IgA, IgD, IgE, IgG, and IgM). IgG Subclass Deficiency is characterized by low serum levels for one or more immunoglobulins, with normal levels of remaining immunoglobulins. IgG is the most abundant immunoglobulin which circulates in the blood. Symptoms tend to be milder for people with IgG Subclass Deficiency, but may include increased susceptibility to respiratory infections.
Learn more about IgG Subclass Deficiency:
- IPEX and IPEX-like syndromes
IPEX Syndrome is caused by mutations in the FOXP3 gene, which is inherited in an X-Linked recessive pattern. This disorder is characterized by the development of autoimmune disease, which affects mostly the intestines, endocrine glands, and skin. Symptoms include enteropathy, severe diarrhea, and failure to thrive. Type 1 Diabetes and Thyroid Disease may also be presenting clinical features of IPEX Syndrome. IPEX-link syndromes present similar symptoms as IPEX Syndrome, but the genetic cause is unknown.
Learn more about IPEX syndromes:
- JAK3 Deficiency
JAK3 Deficiency is a form of Severe Combined Immune Deficiency (SCID), which is inherited in an autosomal recessive pattern. Mutations in the JAK3 gene cause the absence of T cells and Natural Killer cells, and dysfunction in B cells. SCID due to JAK3 Deficiency is characterized by high susceptibility to life-threatening infections, failure to thrive, chronic diarrhea, and graft-versus-host reactions to maternal T cells. This condition is fatal in the first 2 years of life if not treated with a bone marrow transplant.
Learn more about JAK3 Deficiency:
- Leukocyte Adhesion Deficiency
Leukocyte Adhesion Deficiency is characterized by leukocytosis (increased white blood cell count) and recurrent, life-threatening bacterial infections. LAD is often fatal. Infants with LAD have failure to express CD18, a vital immune system component. LAD type II is typically seen in the Middle Eastern population. Bone marrow and stem cell transplantation is an effective therapy for patients with LAD.
Learn more about Leukocyte Adhesion Deficiency:
Leukocyte Adhesion Deficiency-I Clinical Features
- MHC Class II Deficiency
Major Histocompatibility Complex Class II Deficiency, also known as Bare Lymphocyte Syndrome, is a Severe Combined Immune Deficiency (SCID) characterized by a lack of human leucocyte antigen Class II gene expression, absence of humoral and cellular T-cell response to foreign antigens, and impaired antibody production. Patients with MHC Class II Deficiency are lacking CD4 T cells and are susceptible to viral, bacterial, and fungal infections. MHC Class II Deficiency is inherited as an autosomal recessive trait, and is caused by impaired gene regulation.
Learn more about MHC Class II Deficiency:
- Nijmegen Breakage Syndrome
Nijmegen Breakage Syndrome is caused by mutations in the NBN gene inherited in an autosomal recessive pattern. These mutations cause abnormal development of Nibin protein, which causes abnormal response of repairs of DNA damage. This lack of response causes irregular cell division and growth. Nijmegen Breakage Syndrome is characterized by microcephaly, short stature, developmental disabilities, as well as an increased susceptibility to respiratory infections and cancer.
Learn more about Nijmegen Breakage Syndrome:
- NK Cell Deficiency
Natural Killer Cell Deficiencies can be categorized as “classical” and “functional.” Classical NK Cell Deficiencies relate to the quantity of NK cells in the blood, and are caused by mutations in the GATA2 and MCM4 genes. Functional NK Cell Deficiencies relate to the quality of function of NK cells and are caused by mutation in the CD16 gene. NK Deficiencies are characterized by recurring and severe viral infections including Herpes Simplex Virus, Cytomegalovirus, Epstein- Barr Virus, and Human Papilloma Viruses.
Learn more about NK Cell Deficiencies:
- Omenn Syndrome
Omenn Syndrome is a form of Combined Immune Deficiency characterized by high susceptibility to viral, bacterial, and fungal infections, failure to thrive, alopecia, and chronic diarrhea. Omenn Syndrome is inherited in an autosomal recessive pattern. It is a fatal condition if patients are not treated with bone marrow transplantation or hematopoietic stem cell transplantation (HSCT).
Learn more about Omenn Syndrome:
- PFAPA Syndrome
Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis Syndrome (PFAPA) is a syndrome with recurrent episodes of fever, mouth sores, and sore throats. Fevers can last up to 3 to 7 days and occur every few weeks in addition to joint and abdominal pain, rash, headache, vomiting, and diarrhea. This disease can last for several years, but typically resolves itself later in life. Symptoms usually occur during the ages of 2 to 5. Studies show that a tonsillectomy, a removal of the tonsils, cures about 80 percent of patients.
Learn more about PFAPA Syndrome:
- RAG1 and RAG2 Deficiency
RAG1 and RAG2 (recombination activation genes) play an essential role in recombination of immunoglobulin and T-cell receptor genes. These proteins work together to contribute to V(D)J recombination activity, which allows proteins to match antigens present in viruses, bacteria, parasites, and tumor cells. Lack of expression in RAG1 and RAG2 causes dysfunction in this activity, leaving those affected to experience severe infections. Patients with these defects have Severe Combined Immune Deficiency (SCID), with no B- or T-cell function.
Learn more about RAG1 and RAG2 Deficiencies:
- Selective IgA Deficiency
Selective IgA Deficiency is the most common Primary Immunodeficiency. IgA is an essential immunoglobulin in the respiratory and gastrointestinal tracts that plays an important role in developing mucosal immunity and protection against infection. Selective IgA can be characterized by increased incidence of recurrent pneumonias, sinusitis, ear infections, and gastrointestinal infections, and may cause Autoimmune Diseases.
Learn more about Selective IgA Deficiency:
- Severe Combined Immune Deficiency (SCID)
Severe Combined Immune Deficiency (SCID) is a group of disorders characterized by little or no immune response. Also known as the “bubble boy” disease, individuals with SCID are highly susceptible to severe bacterial, viral, and fungal infections. Symptoms include common pneumonias, chicken pox, meningitis, recurrent diarrhea, and failure to thrive. SCID is fatal in the first 2 years of life if not treated with a hematopoietic stem cell transplantation or gene therapy.
Learn more about Severe Combined Immune Deficiency:
- Shwachman-Diamond Syndrome
Shwachman-Diamond Syndrome is caused most frequently by mutations in the SBDS gene, which is inherited in an autosomal recessive pattern. Shwachman- Diamond Syndrome is characterized by dysfunction of the bone marrow, causing neutropenia, which may lead to recurring ear infections and pneumonia. Patients with this syndrome are also more likely to develop anemia and blood cancers (Acute Myeloid Leukemia). Some individuals may also have pancreatic and skeletal abnormalities, as well as complications of the endocrine system.
Learn more about Shwachman-Diamond Syndrome:
- Specific Antibody Deficiency
Specific Antibody Deficiency is characterized by lack of antibodies that assist in fighting off infection. The exact cause and manifestations are not completely known. However, it is hypothesized that Specific Antibody Deficiency causes B cells to not communicate properly with other immune cells for appropriate function. People with Specific Antibody Deficiency may experience increased susceptibility to respiratory tract infections.
Learn more about Specific Antibody Deficiency:
- TACI Deficiency
Transmembrane Activator and Calcium-modulator and Cyclophilin Ligand Interactor (TACI) promotes antibody production and mediates isotype switching in B cells. Deficiencies in TACI cause Common Variable Immunodeficiency (CVID), which is characterized by recurrent infections, especially of the respiratory tract.
Learn more about TACI Deficiency:
- TNF Receptor-Associated Periodic Syndrome (TRAPS)
Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is caused by mutations in the TNFRSF1A gene and is inherited in an autosomal dominant pattern. TNFRSF1A controls signaling patterns that cause cells to initiate inflammation, production of cytokines, and cell death (apoptosis). This condition is characterized by periodic episodes of fevers, which usually last approximately 3 weeks. These episodes can be triggered by stress, infection, and changes in hormones. Other symptoms may include edema, joint pain, and skin rashes. Initial episodes generally occur in infancy and childhood, and can continue throughout adulthood.
Learn more about TRAPS:
- WHIM Syndrome
WHIM syndrome is a rare and difficult-to-diagnose primary immunodeficiency in which the body’s immune system does not function properly and has trouble fighting infections. Some doctors also call primary immunodeficiencies inborn errors of immunity, which are genetic mutations that cause immunodeficiencies. WHIM syndrome is caused by mutations in the CXCR4 gene which causes white blood cells to get trapped in the bone marrow.
WHIM syndrome was named after four symptoms that most diagnosed patients have experienced: Warts, Hypogammaglobulinemia, Infections, Myelokathexis. There are no existing treatments that specifically target the underlying problem of WHIM syndrome—new treatments are needed.
Learn more about WHIM Syndrome:
- Wiskott-Aldrich Syndrome
Most commonly found in males, Wiskott-Aldrich Syndrome is an immune deficiency that reduces the ability for the blood to clot. This abnormality is usually present at birth and leads to bruising easily and episodes of prolonged bleeding after a minor injury. This defect causes many types of white blood cells to be abnormal or nonfunctional, which leads to a risk of several immune and inflammatory disorders.
Learn more about Wiskott-Aldrich Syndrome:
- X-Linked Agammaglobulinemia
X-Linked Agammaglobulinemia (XLA) is a condition that affects 1 in 200,000 newborns, primarily males. These individuals have very few B cells. B cells are specialized white blood cells that help the body protect itself against infection. These cells mature and produce proteins such as antibodies or immunoglobulins. Antibodies are needed to mark foreign germs and infections for destruction. Without these proteins, patients with XLA are extremely susceptible to infection. The most common infections are ear, pneumonia, conjunctivitis, and sinusitis. With treatment, infections can be avoided.
Learn more about X-Linked Agammaglobulinemia:
- X-Linked Lymphoproliferative Disease
X-Linked Lymphoproliferative Disease (XLP) is a disorder of the immune system and blood-forming cells. It is a recessive trait, affecting more males. About 50 percent of these patients that are exposed to Epstein-Barr Virus (EBV), more commonly known as Mononucleosis, tend to develop a plethora of T cells, B cells, and macrophages. This mass production of immune cells causes a life-threatening response known as hemophagocytic lymphohistocytosis, which causes fever, destruction of blood-producing cells in the bone marrow, and liver damage. For some patients, this response can occur without even being exposed to EBV. In addition, abnormal levels of antibodies make these patients prone to many different types of infection and, without allogeneic stem cell transplantation or the replacement of blood-forming cells, many pass away during childhood.
Learn more about X-Linked Lymphoproliferative Disease:
- X-Linked SCID
Affecting at least 1 in every 50,000 to 100,000 male newborns, X-Linked Severe Combined Immune Deficiency (SCID) is the most common form of SCID. This disorder is an inherited defect of the immune system causing a lack of T cells, B cells, and Natural Killer cells. Due to these cell deficiencies, afflicted infants are prone to infections that would not cause illness in a healthy individual, but is life-threatening for a person with X-Linked SCID. Without treatment, patients do not live beyond infancy.
Learn more about X-Linked SCID:
- ZAP-70 Deficiency
ZAP-70 Deficiency is caused by mutations inherited in an autosomal recessive pattern, and presents as a form of Severe Combined Immune Deficiency (SCID). The ZAP-70 gene is involved in T-cell receptor signaling, which plays an essential role in T-cell differentiation and the development of T-cell function. Symptoms include susceptibility to severe bacterial, viral, and opportunistic infections, and failure to thrive. This condition is fatal without hematopoietic stem cell transplantation (HSCT) in the first year of life.
Learn more about ZAP-70 Deficiency:
- γc (IL-2RG) Deficiency
Mutations in the gamma chain of the IL-2 receptor causes an X-Linked Severe Combined Immune Deficiency (SCID) that makes up the majority of all cases of SCID. This condition mostly affects male infants. Symptoms include extreme susceptibility to viral and bacterial infections, thrush, and failure to thrive. SCID is fatal if not treated. Patients may receive bone marrow transplantation or gene therapy as curative treatment.
Learn more about γc Deficiency X-Linked SCID:
Please note that the information contained on these pages is not intended to provide specific medical advice; rather, it is intended for informational purposes only in order to provide a better understanding of these diseases. Please consult with a qualified physician for diagnosis and answers to your questions.