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Types of PI

There are more than 450 primary immunodeficiencies. Explore the definitions and symptoms of some of the most common types.

A

Activated PI3K delta syndrome (APDS)

Activated PI3K delta syndrome (APDS) is a rare primary immunodeficiency (PI) that is often misdiagnosed as CVID or another antibody deficiency.

 

Agammaglobulinemia: X-linked (XLA) and autosomal recessive (ARA)

People with agammaglobulinemia can't produce antibodies, which are an important part of the body's defense against germs.

APECED & APS-1

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type-1 (APS-1) or polyglandular autoimmune (PGA) syndrome type-1, is a primary immunodeficiency disease caused by variants in the autoimmune regulator (AIRE) gene.

 

Ataxia-telangiectasia (A-T)

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder that causes neurological symptoms (like unsteady gait), dilated corkscrew-shaped blood vessels in the white of the eyes and on sun-exposed skin, combined immune deficiency, and high risk of cancer.

Autoimmune lymphoproliferative syndrome (ALPS)

ALPS is a rare genetic disorder in which lymphocytes, a type of white blood cell, increase and accumulate in the spleen and lymph nodes. This is due to the failure of the mechanism that normally causes lymphocytes to die naturally.

B

Bare lymphocyte syndrome type 1 and 2

Bare lymphocyte syndrome type 1 and 2 are forms of combined immune deficiencies (CIDs) characterized by a shortage of major histocompatibility complex (MHC) proteins.

BCL10 deficiency

Deficiency of BCL10 is a rare combined immunodeficiency (CID) associated with severe recurrent infections and autoimmunity.

BCL11A deficiency

BCL11A deficiency is a rare combined immunodeficiency (CID) that causes a profound lack of T cells and risk of invasive infections akin to severe combined immunodeficiency (SCID). Other features include neonatal teeth, umbilical hernia, and skeletal and brain abnormalities.

Bloom syndrome

Bloom syndrome is a type of combined immunodeficiency (CID) caused by a DNA repair defect and primarily described in the Ashkenazi Jewish population.

C

CARD11 deficiency or gain of function

Variants in CARD11 are associated with a spectrum of primary immunodeficiencies. Complete absence of CARD11, which is a rare autosomal recessive condition, causes hypogammaglobulinemia and T cell dysfunction in spite of normal T cell numbers.

Cartilage-hair hypoplasia

Cartilage-hair hypoplasia (CHH) is a skeletal dysplasia sometimes also referred to as immunodeficiency with short-limbed dwarfism. It is caused by mutations in the ribonuclease mitochondrial RNA-processing (RMRP) gene.

CD3G deficiency

Individuals with CD3 gamma deficiency have clinical phenotypes ranging from immune deficiency to immune dysregulation with autoimmunity.

CD70 deficiency

CD70 deficiency is a rare form of combined immunodeficiency with hypogammaglobulinemia and low CD8+ T cells. Individuals are particularly susceptible to chronic Epstein-Barr virus (EBV) and at high risk of EBV-associated lymphoma.

CD8 deficiency

CD8 deficiency is an extremely rare autosomal recessive disorder due to homozygous mutation of CD8 gene.

CHARGE syndrome

CHARGE syndrome is a genetic syndrome with a known pattern of features: coloboma of the eye, heart defects, atresia of the choanae, restriction of growth and development, and ear abnormalities and deafness.

Chronic granulomatous disease (CGD) and other phagocytic cell disorders

Chronic granulomatous disease (CGD) is an inherited disease in which the body’s cells that eat invaders (also called phagocytes) do not make hydrogen peroxide and other chemicals. These chemicals are needed to kill certain bacteria and fungi.

Chronic mucocutaneous candidiasis (CMC)

Chronic mucocutaneous candidiasis (CMC) is characterized by persistent Candida (fungus) infections of the mucous membranes, scalp, skin, and nails.

Chronic neutropenia

People with chronic neutropenia have low levels of white blood cells called neutrophils, and the condition is both a rare blood disorder and a rare type of primary immunodeficiency (PI).

Combined immune deficiency (CID)

Combined immune deficiencies (CID) are a group of primary immunodeficiencies in which both T cells and B cells of the adaptive immune system are either low or function poorly.

Combined immunodeficiency with intestinal atresias

Combined immunodeficiency with intestinal atresias (CID-IA) is a rare, severe disorder in which parts of the small intestine fail to develop properly.

Comel-Netherton syndrome

Comel-Netherton syndrome is a type of hyper IgE syndrome that affects the skin, hair, and immune system.

Common variable immune deficiency (CVID)

Common variable immune deficiency (CVID), previously known as adult-onset hypogammaglobulinemia, is one of the most frequently diagnosed primary immunodeficiencies. It is characterized by low levels of serum antibodies, which cause an increased susceptibility to infection.

Complement deficiencies

Individuals with a complement deficiency can have clinical problems that are a result of the role that the specific complement protein plays in the normal function of the human body.

Congenital athymia

Congenital athymia is an ultra-rare condition in which children are born without a thymus, causing severe immunodeficiency and immune dysregulation.

Coronin 1A deficiency

Coronin 1A deficiency is associated with a very low number of T cells with impaired function, similar to severe combined immunodeficiency (SCID).

CTLA-4 haploinsufficiency and LRBA deficiency

Variants in the genes encoding cytotoxic T lymphocytic antigen-4 (CTLA4) and lipopolysaccharide responsive beige-like anchor (LRBA) can cause immune dysregulation. This means the components of the immune system regulating inflammation, autoimmunity, and cancer lose their proper function, leading to an array of autoimmune disorders and infections.

D

DiGeorge or 22q11.2 deletion syndrome

DiGeorge syndrome, most frequently caused by a deletion at 22q11.2, is a PI caused by abnormal migration and development of certain cells and tissues during fetal development.

DOCK2 deficiency

DOCK2 deficiency is an autosomal recessive disorder associated with early-onset invasive bacterial and viral infections, lymphopenia, and defective T, B, and NK cell function.

E

EXTL3 deficiency

Individuals with this condition can present with severe T cell defects that may mimic severe combined immunodeficiency (SCID) at birth. Additionally, they present with significant bone deformities, such as early fused cranial bones (craniosynostosis) with a small cervical canal, short stature, and abnormally shaped digits.

F

FOXN1 deficiency

Also known as nude/severe combined immunodeficiency (SCID), this rare primary immunodeficiency disrupts adaptive immunity and is characterized by congenital athymia, congenital alopecia totalis, and nail dystrophy.

H

Hemophagocytic lymphohistiocytosis (HLH)

Hemophagocytic lymphohistiocytosis (HLH) occurs when histiocytes and lymphocytes become overactive and attack the body rather than just microorganisms. Familial HLH is a type of PI.

Hoyeraal-Hreidarsson syndrome

This syndrome is a severe form of dyskeratosis congenita with poor growth inside the womb, microcephaly (small head), and pancytopenia (low numbers of all blood cells).

Hyper IgE syndrome

Hyper IgE syndromes (HIES) are rare forms of primary immunodeficiencies (PI) characterized by recurrent eczema, skin abscesses, lung infections, eosinophilia (high numbers of eosinophils in the blood), and high serum levels of immunoglobulin E (IgE). 

Hyper IgM syndromes (HIGM)

Hyper IgM syndromes (HIGM) are characterized by decreased levels of immunoglobulin G (IgG) in the blood and normal or elevated levels of immunoglobulin M (IgM). 

I

IgG subclass deficiency

Patients with persistently low levels of one or two IgG subclasses and a normal total IgG level have a selective IgG subclass deficiency.

IL21 pathway deficiency

Deficiencies of the cytokine, IL-21, and IL21 receptor has been described in children with very early onset inflammatory bowel disease, liver disease, and immunodeficiency with T cell and B cell defects.

Immunodeficiency-centromeric instability facial anomalies (ICF) syndrome

Short for immunodeficiency-centromeric instability facial anomalies syndrome, ICF syndrome is an autosomal recessive disorder that may be due to variants in the ZBTB24, DNMT3B, CDCA7, or HELLS genes.

Innate immune disorders

Innate immune disorders include Myd88 and IRAK-4 deficiencies, TLR3 deficiency, NF-kappa-B essential modulator (NEMO) deficiency syndrome, natural killer (NK) cell deficiency, and disorders in interferon-γ (IFN-γ) and interleukin (IL)-12/23 signaling pathways. 

IPEX syndrome

IPEX is an X-linked disorder in which affected boys develop severe autoimmunity that can target any organ. The gut, skin, and endocrine organs—particularly the pancreas and thyroid gland—are the most common targets.

K

Kabuki syndrome

Kabuki syndrome is a multisystem genetic disorder involving characteristic facial features, growth and developmental delay, and skeletal abnormalities.

L

LCK deficiency

Autosomal recessive disorder due to deficiency of lymphocyte-specific protein-tyrosine kinase (Lck or p56lck), one of the proteins activated upon engagement of the TCR/CD3 complex. Depending on the mutation, individuals may present within the first year of life with variable features.

Leukocyte adhesion deficiency (LAD)

Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency that causes individuals to be abnormally susceptible to developing frequent soft-tissue infections, gum inflammation, and tooth loss.

LICS syndrome

Lung disease, immunodeficiency, and chromosome breakage syndrome (LICS) causes severe, early lung disease.

Ligase 1 deficiency

Individuals with ligase 1 deficiency have high sensitivity to sunlight, stunted growth, developmental delay, and a high predisposition for cancer.

M

MALT1 deficiency

MALT1 deficiency is a combined immunodeficiency that can cause severe eczema, recurrent bacterial and viral infections, inflammatory gastrointestinal disease, long bone fractures, and severe periodontal disease.

Moesin deficiency

Moesin deficiency is an X-linked immunodeficiency associated with lymphopenia, neutropenia, and recurrent bacterial infections.

N

NEMO deficiency syndrome

NEMO deficiency syndrome is a complex disease caused by genetic variants in the X-linked NEMO gene (also known as IKK gamma or IKKG).

Nijmegen breakage syndrome

Variants in the gene that codes for a protein called nibrin cause Nijmegen breakage syndrome (NBS). Affected individuals are highly sensitive to the effects of sunlight and radiation, or any substance that can cause breaks in DNA.

NIK deficiency

NIK deficiency is a rare immunodeficiency resulting in impaired function of T cells, B cells, and natural killer (NK) cells. Affected individuals are susceptible to a wide range of infections.

O

Other antibody deficiency disorders

Individuals with less common antibody deficiencies usually present with upper respiratory infections or infections of the sinuses or lungs. Many of these disorders cause abnormalities in the cells responsible for generating or maintaining an antibody response.

OX40 deficiency

OX40 deficiency is a rare immunodeficiency. CD4+ T cells appear to be dysfunctional in this disorder, whereas antibody production is still intact.

P

Partial RAG1/2 deficiency

"Leaky" variants in RAG1 or RAG2 with residual protein function and T cell production can have a variable presentation, including Omenn syndrome, granulomatous disease, and/or autoimmunity.

PolE/PolE2 deficiency

PolE/PolE2 deficiency is inherited in an autosomal recessive manner. Affected individuals have a high predisposition for infections and decreased numbers of both T and B cells.

Primary immune regulatory disorders (PIRD)

Primary immune regulatory disorders (PIRD) are characterized by a disturbance of immune tolerance and excessive inflammation.

Purine nucleoside phosphorylase deficiency

Purine nucleotide phosphorylase (PNP) deficiency is a rare recessive disorder resulting in moderate to severe immunodeficiency, with reduced T cell numbers and risk of recurrent infections, as well as autoimmune disease.

R

RelB deficiency

RelB deficiency has been found in a small number of individuals with poor T cell and B cell function in spite of normal lymphocyte numbers.

RHOH deficiency

RHOH deficiency is an autosomal recessive disorder caused by variants in the Ras homolog gene family member H (RHOH) gene leading to a defect of T cell function.

RIDDLE syndrome

RIDDLE is short for radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties. It is an autosomal recessive disorder, in which individuals have difficulty repairing DNA damage sustained by the cells.

S

Schimke’s immuno-osseous dysplasia

Schimke’s immuno-osseous dysplasia, an autosomal recessive disorder, is caused by a variant in a gene responsible for chromatin remodeling (SMARCAL1).

Selective IgA deficiency

Selective IgA deficiency is a primary immunodeficiency characterized by an undetectable level of immunoglobulin A (IgA) in the blood and secretions but no other immunoglobulin deficiencies.

Selective IgM deficiency

Individuals with selective IgM deficiency have low levels or lack immunoglobulin M (IgM) but have normal levels of IgA, and IgG. These individuals may have no illness, whereas others develop a variety of illnesses, including infections, allergies, and autoimmunity. 

Severe combined immunodeficiency (SCID)

Severe combined immune deficiency (SCID) is a life-threatening primary immunodeficiency (PI), with a combined absence of T cell and B cell function. There are at least 20 different genetic variants that can cause SCID.

Specific antibody deficiency

Individuals with specific antibody deficiency have normal levels of antibodies (immunoglobulins) but cannot produce antibodies to specific types of microorganisms that cause respiratory infections.

STAT1 and STAT3 gain of function

STAT1 and STAT3 gain of function are autosomal dominant primary immunodeficiencies with significant autoimmunity as a result of immune dysregulation.

STK4 deficiency

The clinical phenotype for STK4 deficiency includes persistent viral infections and bacterial infections. Other reported features include fungal infections, mild eczema, autoimmune cytopenias, and lymphopenia.

T

TCRa deficiency

TCRa deficiency causes susceptibility to recurrent respiratory tract infections, candidiasis, gastroenteritis, and herpesvirus infections, as well as autoimmune symptoms.

TFR1 deficiency

Deficiency of transferrin receptor 1 (TFR1) is a rare, recessive immunodeficiency that causes hypogammaglobulinemia, defective T cell function, intermittent neutropenia and thrombocytopenia, and mild anemia.

Transient hypogammaglobulinemia infancy

When it takes longer than expected for a baby to make their own IgG antibodies, they may have transient hypogammaglobulinemia of infancy (THI).

Tricho-hepato-enteric syndrome

Tricho-hepato-enteric syndrome (THES) is a rare, recessive disorder characterized by chronic diarrhea with poor growth, liver disease, hair and facial abnormalities, and immunodeficiency with impaired antibody function and lymphopenia.

V

Veno-occlusive disease with immunodeficiency

Patients with veno-occlusive disease with immunodeficiency (VODI) have a predisposition to fungal infections, low platelet counts, and enlarged livers.

W

WHIM syndrome

Warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome is an ultra-rare and difficult-to-diagnose primary immunodeficiency (PI) in which individuals are susceptible to life-threatening bacterial infections and to human papillomavirus (HPV) infections.

Wiskott-Aldrich syndrome (WAS)

Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency (PI) that causes bleeding problems and eczema in addition to susceptibility to infections. It is inherited in an X-linked recessive manner.

X

X-linked agammaglobulinemia (XLA)

Use this link for information about agammaglobulinemia (x-linked and autosomal recessive), which is listed under the letter A.

X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia (XMEN)

X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia (XMEN) is seen in boys and is characterized by low CD4 T cells, chronic Epstein-Barr virus (EBV) infections, and lymphoproliferative disorders related to the EBV.

X-linked lymphoproliferative (XLP) syndromes 1 and 2

XLP is characterized by life-long vulnerability to Epstein-Barr virus (EBV) infection, which can lead to severe and fatal infectious mononucleosis, lymph node cancers (lymphomas), and combined immunodeficiency.

Z

ZAP-70 deficiency

ZAP-70 deficiency is a rare autosomal recessive combined immunodeficiency. ZAP-70 plays a crucial role in T cell development and function, and is crucial for CD8 T cell selection. Peripheral T cells from individuals with ZAP-70 deficiency demonstrate defective T cell signaling and have an autoreactive phenotype. Indeed, several individuals have presented with autoimmune disorders.

Resources just for you

PI impacts many lives. If you are living with PI, think you might have PI, are a caregiver, or healthcare professional, these resources may help.

Living with PI

Many people with PI live full lives. Learn how to collaborate with healthcare providers and prioritize your health.

Access tips and tools

Diagnosis

Find out how newborn screening or laboratory and genetic tests are used to reach a diagnosis.

Learn how PI is diagnosed

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