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Immunodeficiency

MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Synonyms: Deficiency Syndrome, Immunologic; Deficiency Syndrome, Immunological; Deficiency Syndromes, Immunologic; Deficiency Syndromes, Immunological; Immunologic Deficiency Syndrome; Immunologic Deficiency Syndromes; Immunological Deficiency Syndrome; Immunological Deficiency Syndromes; Syndrome, Immunologic Deficiency; Syndrome, Immunological Deficiency; Syndromes, Immunologic Deficiency; Syndromes, Immunological Deficiency
SNOMED CT: Immunodeficiency disorder (234532001); Immunodeficiency disease (234532001); Immunodeficiency (234532001)
 
HPO: HP:0002721
Monarch Initiative: MONDO:0021094
OMIM® Phenotypic series: PS300755

Definition

Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVImmunodeficiency

Conditions with this feature

Burkitt lymphoma
MedGen UID:
2377
Concept ID:
C0006413
Neoplastic Process
Burkitt lymphoma is a rare, aggressive B-cell lymphoma that accounts for 30 to 50% of lymphomas in children but only 1 to 2% of lymphomas in adults (Harris and Horning, 2006). It results from chromosomal translocations that involve the MYC gene (190080) and either the lambda or the kappa light chain immunoglobulin genes (147220, 147200). Burkitt lymphoma is causally related to the Epstein-Barr virus (EBV), although the pathogenetic mechanisms are not clear.
Hyper-IgM syndrome type 1
MedGen UID:
96019
Concept ID:
C0398689
Disease or Syndrome
X-linked hyper IgM syndrome (HIGM1), a disorder of abnormal T- and B-cell function, is characterized by low serum concentrations of IgG, IgA, and IgE with normal or elevated serum concentrations of IgM. Mitogen proliferation may be normal, but NK- and T-cell cytotoxicity can be impaired. Antigen-specific responses are usually decreased or absent. Total numbers of B cells are normal but there is a marked reduction of class-switched memory B cells. Defective oxidative burst of both neutrophils and macrophages has been reported. The range of clinical findings varies, even within the same family. More than 50% of males with HIGM1 develop symptoms by age one year, and more than 90% are symptomatic by age four years. HIGM1 usually presents in infancy with recurrent upper- and lower-respiratory tract bacterial infections, opportunistic infections including Pneumocystis jirovecii pneumonia, and recurrent or protracted diarrhea that can be infectious or noninfectious and is associated with failure to thrive. Neutropenia is common; thrombocytopenia and anemia are less commonly seen. Autoimmune and/or inflammatory disorders (such as sclerosing cholangitis) as well as increased risk for neoplasms have been reported as medical complications of this disorder. Significant neurologic complications, often the result of a CNS infection, are seen in 5%-15% of affected males. Liver disease, a serious complication of HIGM1 once observed in more than 80% of affected males by age 20 years, may be decreasing with adequate screening and treatment of Cryptosporidium infection.
Arts syndrome
MedGen UID:
163205
Concept ID:
C0796028
Disease or Syndrome
Arts syndrome, which is part of the spectrum of PRPS1-related disorders, is characterized by profound congenital sensorineural hearing impairment, early-onset hypotonia, delayed motor development, mild to moderate intellectual disability, ataxia, and increased risk of infection, all of which – with the exception of optic atrophy – present before age two years. Signs of peripheral neuropathy develop during early childhood. Twelve of 15 boys from the two Dutch families reported with Arts syndrome died before age six years of complications of infection. Carrier females can show late-onset (age >20 years) hearing impairment and other findings.
Dyskeratosis congenita, X-linked
MedGen UID:
216941
Concept ID:
C1148551
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Progeroid short stature with pigmented nevi
MedGen UID:
224702
Concept ID:
C1261128
Disease or Syndrome
Mulvihill-Smith syndrome is characterized by premature aging, multiple pigmented nevi, lack of facial subcutaneous fat, microcephaly, short stature, sensorineural hearing loss, and mental retardation. Immunodeficiency may also be a feature. Adult manifestations include the development of tumors, a sleep disorder with severe insomnia, and cognitive decline (summary by Yagihashi et al., 2009).
Hyper-IgM syndrome type 2
MedGen UID:
354548
Concept ID:
C1720956
Disease or Syndrome
Hyper-IgM syndrome type 2 (HIGM2) is a rare immunodeficiency characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE, resulting in a profound susceptibility to bacterial infections. For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
Hyper-IgM syndrome type 3
MedGen UID:
328419
Concept ID:
C1720957
Disease or Syndrome
Type 3 immunodeficiency with hyper-IgM (HIGM3), first described in humans by Ferrari et al. (2001), is characterized by hypogammaglobulinemia with normal or elevated levels of IgM. For a general phenotypic description and a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
Hyper-IgM syndrome type 5
MedGen UID:
328420
Concept ID:
C1720958
Disease or Syndrome
Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process. For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
Timothy syndrome
MedGen UID:
331395
Concept ID:
C1832916
Disease or Syndrome
The first identified CACNA1C-related disorder, referred to as Timothy syndrome, consists of the combination of prolonged QT interval, autism, and cardiovascular malformation with syndactyly of the fingers and toes. Infrequent findings also include developmental and speech delay, seizures, and recurrent infections. With increased availability of molecular genetic testing, a wider spectrum of pathogenic variants and clinical findings associated with CACNA1C-related disorders has been recognized. Because CACNA1C is associated with calcium channel function, all individuals with a pathogenic variant in this gene are at risk for cardiac arrhythmia of a specific type. The clinical manifestations of a CACNA1C-related disorder include three phenotypes: Timothy syndrome with or without syndactyly. QT prolongation (QTc >480 ms) and arrhythmias in the absence of other syndromic features. Short QT syndrome (QTc <350 ms) or Brugada syndrome with short QT interval. These three phenotypes can be separated into two broad categories on the basis of the functional consequences of the pathogenic variants in CACNA1C: QT prolongation with or without a Timothy syndrome-associated phenotype associated with pathogenic variants inducing a gain of function at the cellular level (i.e., increased calcium current). Short QT interval with or without Brugada syndrome EKG pattern associated with pathogenic variants causing loss of function (i.e., reduced calcium current).
Metaphyseal dysplasia without hypotrichosis
MedGen UID:
320444
Concept ID:
C1834821
Disease or Syndrome
The cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders are a continuum that includes the following phenotypes: Metaphyseal dysplasia without hypotrichosis (MDWH). Cartilage-hair hypoplasia (CHH). Anauxetic dysplasia (AD). CHH-AD spectrum disorders are characterized by severe disproportionate (short-limb) short stature that is usually recognized in the newborn, and occasionally prenatally because of the short extremities. Other findings include joint hypermobility, fine silky hair, immunodeficiency, anemia, increased risk for malignancy, gastrointestinal dysfunction, and impaired spermatogenesis. The most severe phenotype, AD, has the most pronounced skeletal phenotype, may be associated with atlantoaxial subluxation in the newborn, and may include cognitive deficiency. The clinical manifestations of the CHH-AD spectrum disorders are variable, even within the same family.
Primary immunodeficiency syndrome due to p14 deficiency
MedGen UID:
372135
Concept ID:
C1835829
Disease or Syndrome
Primary immunodeficiency syndrome due to p14 deficiency is characterised by short stature, hypopigmentation, coarse facies and frequent bronchopulmonary <i>Streptococcus pneumoniae</i> infections.
Griscelli syndrome type 3
MedGen UID:
373124
Concept ID:
C1836573
Disease or Syndrome
Griscelli syndrome type 3 (GS3) is a rare autosomal recessive disorder that results in a characteristic pigmentary dilution of the skin and hair, which shows a silvery-gray sheen associated with large clumps of pigment in hair shafts and an abnormal accumulation of end-stage melanosomes in the center of melanocytes. There are no immunologic or neurologic manifestations (summary by Menasche et al., 2003). For a discussion of phenotypic and genetic heterogeneity in Griscelli syndrome, see GS1 (214450).
Immune deficiency, familial variable
MedGen UID:
374426
Concept ID:
C1840266
Disease or Syndrome
Hyper-IgM syndrome type 4
MedGen UID:
330847
Concept ID:
C1842413
Disease or Syndrome
Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process (summary by Imai et al., 2003). For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
Immunodeficiency 67
MedGen UID:
375137
Concept ID:
C1843256
Disease or Syndrome
Immunodeficiency-67 (IMD67) is an autosomal recessive primary immunodeficiency characterized by recurrent severe systemic and invasive bacterial infections beginning in infancy or early childhood. The most common organisms implicated are Streptococcus pneumoniae and Staphylococcus aureus; Pseudomonas and atypical Mycobacteria may also be observed. IMD67 is life-threatening in infancy and early childhood. The first invasive infection typically occurs before 2 years of age, with meningitis representing up to 41% of the bacterial infections. The mortality rate in early childhood is high, with most deaths occurring before 8 years of age. Affected individuals have an impaired inflammatory response to infection, including lack of fever and neutropenia, although erythrocyte sedimentation rate (ESR) and C-reactive protein may be elevated. General immunologic workup tends to be normal, with normal levels of B cells, T cells, and NK cells. However, more detailed studies indicate impaired cytokine response to lipopolysaccharide (LPS) and IL1B (147720) stimulation; response to TNFA (191160) is usually normal. Patients have good antibody responses to most vaccinations, with the notable exception of pneumococcal vaccination. Viral, fungal, and parasitic infections are not generally observed. Early detection is critical in early childhood because prophylactic treatment with IVIg or certain antibiotics is effective; the disorder tends to improve naturally around adolescence. At the molecular level, the disorder results from impaired function of selective Toll receptor (see TLR4, 603030)/IL1R (see IL1R1, 147810) signaling pathways that ultimately activate NFKB (164011) to produce cytokines (summary by Ku et al., 2007; Picard et al., 2010; Grazioli et al., 2016). See also IMD68 (612260), caused by mutation in the MYD88 gene (602170), which shows a similar phenotype to IMD67. As the MYD88 and IRAK4 genes interact in the same intracellular signaling pathway, the clinical and cellular features are almost indistinguishable (summary by Picard et al., 2010).
Granulomatous disease, chronic, X-linked
MedGen UID:
336165
Concept ID:
C1844376
Disease or Syndrome
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis). Granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. While CGD may present anytime from infancy to late adulthood, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival.
X-linked lymphoproliferative disease due to XIAP deficiency
MedGen UID:
336848
Concept ID:
C1845076
Disease or Syndrome
X-linked lymphoproliferative disease (XLP) has two recognizable subtypes, XLP1 and XLP2. XLP1 is characterized predominantly by one of three commonly recognized phenotypes: Inappropriate immune response to Epstein-Barr virus (EBV) infection leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis. Dysgammaglobulinemia. Lymphoproliferative disease (malignant lymphoma). XLP2 is most often characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease. HLH resulting from EBV infection is associated with an unregulated and exaggerated immune response with widespread proliferation of cytotoxic T cells, EBV-infected B cells, and macrophages. Dysgammaglobulinemia is typically hypogammaglobulinemia of one or more immunoglobulin subclasses. The malignant lymphomas are typically B-cell lymphomas, non-Hodgkin type, often extranodal, and in particular involving the intestine.
Ectodermal dysplasia and immunodeficiency 1
MedGen UID:
375787
Concept ID:
C1846008
Disease or Syndrome
Ectodermal dysplasia with immunodeficiency-1 (EDAID1) is an X-linked recessive disorder that characteristically affects only males. Affected individuals have onset of recurrent severe infections due to immunodeficiency in early infancy or in the first years of life. There is increased susceptibility to bacterial, pneumococcal, mycobacterial, and fungal infections. Laboratory studies usually show dysgammaglobulinemia with low IgG subsets and normal or increased IgA and IgM, consistent with impaired 'class-switching' of B cells, although immunologic abnormalities may be subtle compared to the clinical picture, and B- and T-cell numbers are usually normal. There is a poor antibody response to polysaccharide vaccinations, particularly pneumococcus; response to other vaccinations is variable. Patients also have features of ectodermal dysplasia, including conical incisors, hypo/anhidrosis, and thin skin or hair. Severely affected individuals may also show lymphedema, osteopetrosis, and, rarely, hematologic abnormalities. The phenotype is highly variable, likely due to different hypomorphic mutations, and may be fatal in childhood. Intravenous immunoglobulins and prophylactic antibiotics are used as treatment; some patients may benefit from bone marrow transplantation. Although only males tend to be affected with immunodeficiency, many patients inherit a mutation from a mother who has mild features of IP or conical teeth (summary by Doffinger et al., 2001, Orange et al., 2004, Roberts et al., 2010, Heller et al., 2020). Genetic Heterogeneity of Ectodermal Dysplasia and Immune Deficiency Also see EDAID2 (612132), caused by mutation in the NFKBIA gene (164008).
Immunodeficiency due to CD25 deficiency
MedGen UID:
377894
Concept ID:
C1853392
Disease or Syndrome
Immunodeficiency-41 is an autosomal recessive complex disorder of immune dysregulation. Affected individuals present in infancy with recurrent viral, fungal, and bacterial infections, lymphadenopathy, and variable autoimmune features, such as autoimmune enteropathy and eczematous skin lesions. Immunologic studies show a defect in T-cell regulation (summary by Goudy et al., 2013).
Immunodeficiency, partial combined, with absence of HLA Determinants and beta-2-microglobulin from lymphocytes
MedGen UID:
340957
Concept ID:
C1855762
Disease or Syndrome
Vici syndrome
MedGen UID:
340962
Concept ID:
C1855772
Disease or Syndrome
With the current widespread use of multigene panels and comprehensive genomic testing, it has become apparent that the phenotypic spectrum of EPG5-related disorder represents a continuum. At the most severe end of the spectrum is classic Vici syndrome (defined as a neurodevelopmental disorder with multisystem involvement characterized by the combination of agenesis of the corpus callosum, cataracts, hypopigmentation, cardiomyopathy, combined immunodeficiency, microcephaly, and failure to thrive); at the milder end of the spectrum are attenuated neurodevelopmental phenotypes with variable multisystem involvement. Median survival in classic Vici syndrome appears to be 24 months, with only 10% of children surviving longer than age five years; the most common causes of death are respiratory infections as a result of primary immunodeficiency and/or cardiac insufficiency resulting from progressive cardiac failure. No data are available on life span in individuals at the milder end of the spectrum.
Hepatic veno-occlusive disease-immunodeficiency syndrome
MedGen UID:
344659
Concept ID:
C1856128
Disease or Syndrome
Hepatic veno-occlusive disease with immunodeficiency (VODI) is characterized by: (1) primary immunodeficiency; and (2) terminal hepatic lobular vascular occlusion and hepatic fibrosis manifest as hepatomegaly and/or hepatic failure. Onset is usually before age six months. The immunodeficiency comprises severe hypogammaglobulinemia, clinical evidence of T-cell immunodeficiency with normal numbers of circulating T cells, absent lymph node germinal centers, and absent tissue plasma cells. Bacterial and opportunistic infections including Pneumocystis jirovecii infection, mucocutaneous candidiasis, and enteroviral or cytomegalovirus infections occur. In the past the prognosis for affected individuals was poor, with 100% mortality in the first year of life if unrecognized and untreated with intravenous immunoglobulin (IVIG) and Pneumocystis jirovecii prophylaxis. However, with early recognition and treatment there is a marked improvement in prognosis.
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2
MedGen UID:
383869
Concept ID:
C1856245
Disease or Syndrome
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis). Granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. While CGD may present anytime from infancy to late adulthood, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival.
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1
MedGen UID:
341102
Concept ID:
C1856251
Disease or Syndrome
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis). Granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. While CGD may present anytime from infancy to late adulthood, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival.
Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative
MedGen UID:
383872
Concept ID:
C1856255
Disease or Syndrome
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis). Granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. While CGD may present anytime from infancy to late adulthood, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival.
Granulocytopenia with immunoglobulin abnormality
MedGen UID:
383874
Concept ID:
C1856263
Disease or Syndrome
Immunodeficiency-59 and hypoglycemia (IMD59) is an autosomal recessive primary immunologic disorder characterized by combined immunodeficiency and recurrent septic infections of the respiratory tract, skin, and mucous membranes, as well as disturbed glucose metabolism. Granulocytopenia and B-cell and dendritic cell deficiency are present (Haapaniemi et al., 2017).
Immunodeficiency 25
MedGen UID:
346666
Concept ID:
C1857798
Disease or Syndrome
Any severe combined immunodeficiency in which the cause of the disease is a mutation in the CD247 gene.
Chondroitin-6-sulfaturia, defective cellular immunity, nephrotic syndrome
MedGen UID:
349095
Concept ID:
C1859104
Disease or Syndrome
Predisposition to invasive fungal disease due to CARD9 deficiency
MedGen UID:
347128
Concept ID:
C1859353
Disease or Syndrome
A rare genetic primary immunodeficiency with characteristics of increased susceptibility to fungal infections that typically manifest as recurrent, chronic mucocutaneous candidiasis, systemic candidiasis with meningoencephalitis and deep dermatophytosis. Dermatophytes invade skin, hair, nails, lymph nodes and brain, resulting in erythematosquamous lesions, nodular subcutaneous or ulcerative infiltrations, severe onychomycosis and lymphadenopathy.
Hyperzincemia with functional zinc depletion
MedGen UID:
356415
Concept ID:
C1865986
Disease or Syndrome
4p partial monosomy syndrome
MedGen UID:
408255
Concept ID:
C1956097
Disease or Syndrome
Wolf-Hirschhorn syndrome is a congenital malformation syndrome characterized by pre- and postnatal growth deficiency, developmental disability of variable degree, characteristic craniofacial features ('Greek warrior helmet' appearance of the nose, high forehead, prominent glabella, hypertelorism, high-arched eyebrows, protruding eyes, epicanthal folds, short philtrum, distinct mouth with downturned corners, and micrognathia), and a seizure disorder (Battaglia et al., 2008).
Immunodeficiency 35
MedGen UID:
409751
Concept ID:
C1969086
Disease or Syndrome
Immunodeficiency-35 (IMD35) is an autosomal recessive primary immunodeficiency characterized by increased susceptibility to localized or disseminated mycobacterial infection after BCG vaccination. Some patients may have increased susceptibility to infection with other intracellular organisms and/or viral infections. Fungal infections are not observed. Laboratory studies show normal levels of immune cells but defective signaling in specific immunologic pathways (summary by Kreins et al., 2015).
Immunodeficiency 33
MedGen UID:
370376
Concept ID:
C1970879
Disease or Syndrome
Immunodeficiency-33 (IMD33) is an X-linked recessive disorder that affects only males. It is characterized by early-onset severe infections, usually due to pneumococcus, H. influenzae, and atypical mycobacteria, although other organisms have also been detected. Immunologic investigations may show variable abnormalities or may be normal. Disturbances include dysgammaglobulinemia with hypogammaglobulinemia, decreased IgG2, aberrant levels of IgM and IgA, and decreased class-switched memory B cells. There is often poor, but variable, response to vaccination; in particular, most patients do not develop antibodies to certain polysaccharide vaccines, notably pneumococcus. Other immunologic abnormalities may include impaired NK cytotoxic function, impaired cytokine production upon stimulation with IL1B (147720) or TNFA (191160), low IL6 (147620), low IL12 (see 161561), and decreased IFNG (147570). Patients do not have overt abnormalities of T-cell proliferation, although signaling pathways, such as CD40LG (300386)/CD40 (109535), may be disturbed. There is heterogeneity in the immunologic phenotype, resulting in highly variable clinical courses, most likely due to the different effects of hypomorphic mutations. Treatment with antibiotics and IVIg is usually beneficial; hematopoietic stem cell transplantation may not be necessary, but can be effective. Features of hypohidrotic ectodermal dysplasia are generally not present, although some patients may have conical teeth or hypodontia (summary by Orange et al., 2004, Filipe-Santos et al., 2006, Salt et al., 2008, Heller et al., 2020).
RIDDLE syndrome
MedGen UID:
394368
Concept ID:
C2677792
Disease or Syndrome
RIDDLE is an acronym for the major features of this syndrome: radiosensitivity, immunodeficiency, dysmorphic facies, and learning difficulties (Stewart et al., 2007).
Combined immunodeficiency due to STIM1 deficiency
MedGen UID:
440575
Concept ID:
C2748557
Disease or Syndrome
Immunodeficiency-10 (IMD10) is an autosomal recessive primary immunodeficiency characterized by onset of recurrent infections in childhood due to defective T- and NK-cell function, although the severity is variable. Affected individuals may also have hypotonia, hypohidrosis, or dental enamel hypoplasia consistent with amelogenesis imperfecta (summary by Parry et al., 2016).
Combined immunodeficiency due to ORAI1 deficiency
MedGen UID:
440578
Concept ID:
C2748568
Disease or Syndrome
Immunodeficiency-9 (IMD9) is an autosomal recessive disorder characterized by early onset of recurrent infections due to defective T-cell activation. Affected individuals also have congenital myopathy resulting in muscle weakness as well as features of ectodermal dysplasia, including soft dental enamel (summary by McCarl et al., 2009).
Immunodeficiency, common variable, 1
MedGen UID:
460728
Concept ID:
C3149378
Disease or Syndrome
Common variable immunodeficiency (CVID) is a clinically and genetically heterogeneous group of disorders characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections, and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B cells are usually in the normal range, but can be low. Most individuals with CVID have onset of infections after age 10 years. CVID represents the most common form of primary immunodeficiency disorders and is the most common form of primary antibody deficiency. Approximately 10 to 20% of patients with a diagnosis of CVID have a family history of the disorder (reviews by Chapel et al., 2008, Conley et al., 2009, and Yong et al., 2009). Genetic Heterogeneity of Common Variable Immunodeficiency Common variable immunodeficiency is a genetically heterogeneous disorder. See also CVID2 (240500), caused by mutation in the TACI gene (TNFRSF13B; 604907); CVID3 (613493), caused by mutation in the CD19 gene (107265); CVID4 (613494), caused by mutation in the BAFFR gene (TNFRSF13C; 606269); CVID5 (613495), caused by mutation in the CD20 gene (112210); CVID6 (613496), caused by mutation in the CD81 gene (186845); CVID7 (614699), caused by mutation in the CD21 gene (CR2; 120650); CVID8 (614700), caused by mutation in the LRBA gene (606453); CVID10 (615577), caused by mutation in the NFKB2 gene (164012); CVID11 (615767), caused by mutation in the IL21 gene (605384); CVID12 (616576), caused by mutation in the NFKB1 gene (164011); CVID13 (616873), caused by mutation in the IKZF1 gene (603023); CVID14 (617765), caused by mutation in the IRF2BP2 gene (615332); and CVID15 (620670), caused by heterozygous mutation in the SEC61A1 gene (609213). The disorder formerly designated CVID9 has been found to be a form of autoimmune lymphoproliferative disorder; see ALPS3 (615559).
Lung fibrosis-immunodeficiency-46,XX gonadal dysgenesis syndrome
MedGen UID:
461506
Concept ID:
C3150156
Disease or Syndrome
Lung fibrosis-immunodeficiency-46,XX gonadal dysgenesis syndrome is characterised by immune deficiency, gonadal dysgenesis and fatal lung fibrosis. So far, it has been described in two sisters born to consanguineous parents. Both karyotypes were normal female (46,XX). No genetic anomalies could be identified by comparative genome hybridization analysis of their genomes or by analysis of genes known to be associated with these types of anomalies.
X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia
MedGen UID:
477076
Concept ID:
C3275445
Disease or Syndrome
XMEN is an X-linked recessive immunodeficiency characterized by CD4 (186940) lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation (Li et al., 2011). Affected individuals have chronic Epstein-Barr virus (EBV) infection and are susceptible to the development of EBV-associated B-cell lymphoproliferative disorders. Magnesium supplementation may be therapeutic (summary by Li et al., 2014).
Immunodeficiency-centromeric instability-facial anomalies syndrome 2
MedGen UID:
481378
Concept ID:
C3279748
Disease or Syndrome
Immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disorder characterized by facial dysmorphism, immunoglobulin deficiency resulting in recurrent infections, and mental retardation. Laboratory studies of patient cells show hypomethylation of satellite regions of chromosomes 1, 9, and 16, as well as pericentromeric chromosomal instability in response to phytohemagglutinin stimulation (summary by de Greef et al., 2011). For a discussion of genetic heterogeneity of immunodeficiency-centromeric instability-facial anomalies syndrome, see ICF1 (242860).
Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome
MedGen UID:
481620
Concept ID:
C3279990
Disease or Syndrome
IMD31C is a disorder of immunologic dysregulation with highly variable manifestations resulting from autosomal dominant gain-of-function mutations in STAT1 (600555). Most patients present in infancy or early childhood with chronic mucocutaneous candidiasis (CMC). Other highly variable features include recurrent bacterial, viral, fungal, and mycoplasmal infections, disseminated dimorphic fungal infections, enteropathy with villous atrophy, and autoimmune disorders, such as hypothyroidism or diabetes mellitus. A subset of patients show apparently nonimmunologic features, including osteopenia, delayed puberty, and intracranial aneurysms. Laboratory studies show increased activation of gamma-interferon (IFNG; 147570)-mediated inflammation (summary by Uzel et al., 2013 and Sampaio et al., 2013).
Monocytopenia with susceptibility to infections
MedGen UID:
481660
Concept ID:
C3280030
Disease or Syndrome
This primary immunodeficiency, designated IMD21, DCML, or MONOMAC, is characterized by profoundly decreased or absent monocytes, B lymphocytes, natural killer (NK) lymphocytes, and circulating and tissue dendritic cells (DCs), with little or no effect on T-cell numbers. Clinical features of IMD21 are variable and include susceptibility to disseminated nontuberculous mycobacterial infections, papillomavirus infections, opportunistic fungal infections, and pulmonary alveolar proteinosis. Bone marrow hypocellularity and dysplasia of myeloid, erythroid, and megakaryocytic lineages are present in most patients, as are karyotypic abnormalities, including monosomy 7 and trisomy 8. In the absence of cytogenetic abnormalities or overt dysplasia, hypoplastic bone marrow may initially be diagnosed as aplastic anemia. Bone marrow transplantation is the only cure. Some patients may have an increased risk of miscarriage. Both autosomal dominant transmission and sporadic cases occur. Less common manifestations of GATA2 deficiency include lymphedema and sensorineural hearing loss, a phenotype usually termed 'Emberger syndrome' (614038) (summary by Bigley et al. (2011), Hsu et al. (2011), and Spinner et al. (2014)).
Trichohepatoenteric syndrome 2
MedGen UID:
482919
Concept ID:
C3281289
Disease or Syndrome
Trichohepatoenteric syndrome (THES), generally considered to be a neonatal enteropathy, is characterized by intractable diarrhea (seen in almost all affected children), woolly hair (seen in all), intrauterine growth restriction, facial dysmorphism, and short stature. Additional findings include poorly characterized immunodeficiency, recurrent infections, skin abnormalities, and liver disease. Mild intellectual disability (ID) is seen in about 50% of affected individuals. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported.
Combined immunodeficiency due to LRBA deficiency
MedGen UID:
766426
Concept ID:
C3553512
Disease or Syndrome
Common variable immunodeficiency-8 with autoimmunity is an autosomal recessive disorder of immune dysregulation. Affected individuals have early childhood onset of recurrent infections, particularly respiratory infections, and also develop variable autoimmune disorders, including idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and inflammatory bowel disease. The presentation and phenotype are highly variable, even within families (summary by Lopez-Herrera et al., 2012 and Alangari et al., 2012). Immunologic findings are also variable and may include decreased B cells, hypogammaglobulinemia, and deficiency of CD4+ T regulatory (Treg) cells (Charbonnier et al., 2015). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
Combined immunodeficiency due to STK4 deficiency
MedGen UID:
766857
Concept ID:
C3553943
Disease or Syndrome
Immunodeficiency-110 (IMD110) is an autosomal recessive primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, and autoimmune manifestations. Patients are at risk for developing lymphoproliferative disorders or lymphoma, particularly associated with EBV. Some patients may show cardiac malformations, including atrial septal defect (Abdollahpour et al., 2012; Nehme et al., 2012).
Facial dysmorphism-immunodeficiency-livedo-short stature syndrome
MedGen UID:
767490
Concept ID:
C3554576
Disease or Syndrome
FILS syndrome is characterized by mild facial dysmorphism, mainly malar hypoplasia, livedo on the skin since birth, immunodeficiency resulting in recurrent infections, and short stature (summary by Pachlopnik Schmid et al., 2012).
Dyskeratosis congenita, autosomal recessive 5
MedGen UID:
767570
Concept ID:
C3554656
Disease or Syndrome
Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Severe combined immunodeficiency due to CARD11 deficiency
MedGen UID:
767600
Concept ID:
C3554686
Disease or Syndrome
Immunodeficiency-11A is an autosomal recessive primary immunodeficiency characterized by normal numbers of T and B lymphocytes, but defective intracellular signaling. There is a block in B-cell differentiation with increased numbers of transitional B cells and hypogammaglobulinemia, as well as decreased numbers of regulatory T cells and defects in T-cell function (summary by Greil et al., 2013 and Stepensky et al., 2013).
Cryptosporidiosis-chronic cholangitis-liver disease syndrome
MedGen UID:
767601
Concept ID:
C3554687
Disease or Syndrome
Immunodeficiency-56 is an autosomal recessive primary immunodeficiency characterized by B- and T-cell defects and variable dysfunction of NK cells. Patients tend to have normal numbers of lymphocytes, but show defective class-switched B cells, low IgG, defective antibody response, and defective T-cell responses to certain antigens (summary by Kotlarz et al., 2013).
Immunodeficiency 14
MedGen UID:
811535
Concept ID:
C3714976
Disease or Syndrome
Activated PI3K-delta syndrome (also known as APDS) is a disorder that impairs the immune system. Individuals with this condition often have low numbers of white blood cells (lymphopenia), particularly B cells and T cells. Normally, these cells recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. The severity of activated PI3K-delta syndrome varies widely. Some people may have multiple, severe infections while others show mild symptoms to none at all.\n\nMost commonly, people with activated PI3K-delta syndrome develop recurrent infections that begin in childhood, particularly in the lungs, sinuses, and ears. Over time, recurrent respiratory tract infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. People with activated PI3K-delta syndrome may also have chronic active viral infections, such as Epstein-Barr virus, herpes simplex virus, or cytomegalovirus infections.\n\nThere are two types of activated PI3K-delta syndrome, each with different genetic causes.\n\nAnother possible feature of activated PI3K-delta syndrome is abnormal clumping of white blood cells. These clumps can lead to enlarged lymph nodes (lymphadenopathy) or an enlarged spleen (splenomegaly). The white blood cells can also build up to form solid masses (nodular lymphoid hyperplasia), usually in the moist lining of the airways or intestines. While nodular lymphoid hyperplasia is not cancerous (benign), activated PI3K-delta syndrome increases the risk of developing forms of blood cancer called Hodgkin lymphoma and non-Hodgkin lymphoma.\n\nSome people with activated PI3K-delta syndrome develop autoimmunity, which occurs when the body attacks its own tissues and organs by mistake.
Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency
MedGen UID:
814919
Concept ID:
C3808589
Disease or Syndrome
Autosomal dominant IRF8 deficiency, or IMD32A, causes an abnormal peripheral blood myeloid phenotype with a marked loss of CD11C (ITGAX; 151510)-positive/CD1C (188340)-positive dendritic cells, resulting in selective susceptibility to mycobacterial infections (Hambleton et al., 2011).
Severe combined immunodeficiency due to CORO1A deficiency
MedGen UID:
815713
Concept ID:
C3809383
Disease or Syndrome
Immunodeficiency-8 with lymphoproliferation (IMD8) is an autosomal recessive primary immunodeficiency characterized by early-childhood onset of recurrent infections and lymphoproliferative disorders, often associated with EBV infection. Laboratory studies show defects in the numbers and function of certain lymphocyte subsets, particularly T cells (Moshous et al., 2013; Stray-Pedersen et al., 2014).
Combined immunodeficiency due to MALT1 deficiency
MedGen UID:
815913
Concept ID:
C3809583
Disease or Syndrome
Combined immunodeficiency due to MALT1 deficiency is a rare, genetic form of primary immunodeficiency characterized by growth retardation, early recurrent pulmonary infections leading to bronchiectasis, inflammatory gastrointestinal disease, and other symptoms, such as rash, dermatitis, skin infections.
Idiopathic CD4 lymphocytopenia
MedGen UID:
816098
Concept ID:
C3809768
Disease or Syndrome
Idiopathic CD4 lymphopenia (ICL) is a rare and heterogeneous syndrome defined by a reproducible reduction in the CD4 T-lymphocyte count (less than 300 cells per microliter or less than 20% of total T cells) in the absence of HIV infection or other known causes of immunodeficiency. ICL predisposes to infections and malignancy (summary by Gorska and Alam, 2012).
Combined immunodeficiency due to OX40 deficiency
MedGen UID:
816383
Concept ID:
C3810053
Disease or Syndrome
Immunodeficiency-16 is an autosomal recessive primary immunodeficiency associated with classic Kaposi sarcoma of childhood and poor T-cell recall immune responses due to complete functional OX40 deficiency (Byun et al., 2013).
Combined immunodeficiency due to CD3gamma deficiency
MedGen UID:
816437
Concept ID:
C3810107
Disease or Syndrome
Immunodeficiency-17 (IMD17) is an autosomal recessive primary immunodeficiency characterized by highly variable clinical severity. Some patients have onset of severe recurrent infections in early infancy that may be lethal, whereas others may be only mildly affected or essentially asymptomatic into young adulthood. More severely affected patients may have evidence of autoimmune disease or enteropathy. The immunologic pattern is similar among patients, showing partial T-cell lymphopenia, particularly of cytotoxic CD8 (see 186910)-positive cells, decreased amounts of the CD3 complex, and impaired proliferative responses to T-cell receptor (TCR)-dependent stimuli. B cells, natural killer (NK) cells, and immunoglobulins are usually normal. Although thymic output of functional naive T cells early in life is decreased, polyclonal expansion of functional memory T cells is substantial. The phenotype in some patients is reminiscent of severe combined immunodeficiency (SCID) (summary by Timon et al. (1993) and Recio et al. (2007)).
Immunodeficiency 18
MedGen UID:
816457
Concept ID:
C3810127
Disease or Syndrome
Immunodeficiency-18 is an autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18 (summary by de Saint Basile et al., 2004).
Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity
MedGen UID:
816672
Concept ID:
C3810342
Disease or Syndrome
Immunodeficiency-20 is a rare autosomal recessive primary immunodeficiency characterized by functional deficiency of NK cells. Patient NK cells are defective in spontaneous cell cytotoxicity, but retain antibody-dependent cellular cytotoxicity. Patients typically present early in childhood with severe herpes viral infections, particularly Epstein Barr virus (EBV), and human papillomavirus (HPV) (summary by Grier et al., 2012).
Vasculitis due to ADA2 deficiency
MedGen UID:
854497
Concept ID:
C3887654
Disease or Syndrome
Adenosine deaminase 2 deficiency (DADA2) is a complex systemic autoinflammatory disorder in which vasculopathy/vasculitis, dysregulated immune function, and/or hematologic abnormalities may predominate. Inflammatory features include intermittent fevers, rash (often livedo racemosa/reticularis), and musculoskeletal involvement (myalgia/arthralgia, arthritis, myositis). Vasculitis, which usually begins before age ten years, may manifest as early-onset ischemic (lacunar) and/or hemorrhagic strokes, or as cutaneous or systemic polyarteritis nodosa. Hypertension and hepatosplenomegaly are often found. More severe involvement may lead to progressive central neurologic deficits (dysarthria, ataxia, cranial nerve palsies, cognitive impairment) or to ischemic injury to the kidney, intestine, and/or digits. Dysregulation of immune function can lead to immunodeficiency or autoimmunity of varying severity; lymphadenopathy may be present and some affected individuals have had lymphoproliferative disease. Hematologic disorders may begin early in life or in late adulthood, and can include lymphopenia, neutropenia, pure red cell aplasia, thrombocytopenia, or pancytopenia. Of note, both interfamilial and intrafamilial phenotypic variability (e.g., in age of onset, frequency and severity of manifestations) can be observed; also, individuals with biallelic ADA2 pathogenic variants may remain asymptomatic until adulthood or may never develop clinical manifestations of DADA2.
Immunodeficiency 28
MedGen UID:
862384
Concept ID:
C4013947
Disease or Syndrome
IMD28 is caused by autosomal recessive (AR) IFNGR2 deficiency, a rare molecular cause of susceptibility to mycobacterial disease. The clinical presentation of complete AR IFNGR2 deficiency resembles that of complete IFNGR1 deficiency (IMD27A; 209950). The disease manifests early in life, with severe, often fatal, infection. The most commonly encountered pathogens include M. bovis bacillus Calmette-Guerin (BCG), M. avium, and M. fortuitum. Complete AR IFNGR2 deficiency is characterized by an undetectable cellular response to interferon-gamma (IFNG; 147570). There is also a rare partial form of AR IFNGR2 deficiency, reported in 1 child, who retained a residual cellular response to IFNG and presented with a relatively mild infection by M. bovis BCG and M. abscessus (review by Al-Muhsen and Casanova, 2008).
Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency
MedGen UID:
862385
Concept ID:
C4013948
Disease or Syndrome
IMD29 results from autosomal recessive IL12B deficiency and is characterized by undetectable IL12B secretion from leukocytes. IL12B-deficient patients generally present with bacillus Calmette-Guerin (BCG) disease after vaccination in childhood, and at least half also have Salmonella infection. Infections with Mycobacterium tuberculosis and environmental mycobacteria have also been reported in IL12B-deficient patients. The phenotype is relatively mild, and patients have a good prognosis (review by Al-Muhsen and Casanova, 2008).
Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency
MedGen UID:
862386
Concept ID:
C4013949
Disease or Syndrome
IMD30 results from autosomal recessive IL12RB1 deficiency and is the most common form of susceptibility to mycobacterial disease. Activated T and natural killer lymphocytes from IMD30 patients do not express IL12RB1 on their surface or, more rarely, express nonfunctional IL12RB1 on their surface. IMD30 patients therefore lack responses to IL12 (see 161560) and IL23 (see 605580). The clinical presentation of IL12RB1-deficient patients is similar to that of IL12B-deficient patients (see IMD29, 614890). Bacillus Calmette-Guerin (BCG) disease and salmonellosis are the most frequent infections. Salmonellosis is present in about half of IL12RB1-deficient patients, and significant numbers of patients present with isolated salmonellosis. Severe tuberculosis has been reported in several unrelated patients, and other infections have been reported in single patients. IMD30 has low penetrance, and patients have relatively mild disease and good prognosis (review by Al-Muhsen and Casanova, 2008).
Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency
MedGen UID:
862387
Concept ID:
C4013950
Disease or Syndrome
Immunodeficiency-31A (IMD31A) results from autosomal dominant (AD) STAT1 deficiency. STAT1 is crucial for cellular responses to IFNA (147660)/IFNB (147640) (type I interferon) and IFNG (147570) (type III interferon). AD STAT1 deficiency selectively affects the IFNG pathway, but not the IFNA/IFNB pathway, and confers a predisposition to mycobacterial infections. Pathogens reported in IMD31A patients include bacillus Calmette-Guerin (BCG) and Mycobacterium avium complex, as well as Mycobacterium tuberculosis. IMD31A has low penetrance and a mild clinical phenotype with good prognosis for recovery (review by Al-Muhsen and Casanova, 2008). Two patients with heterozygous STAT1 mutations have been reported with increased susceptibility to adult-onset herpes simplex encephalitis (HSE) without a history of other significant infections (Mork et al., 2015).
Severe combined immunodeficiency due to LCK deficiency
MedGen UID:
862670
Concept ID:
C4014233
Disease or Syndrome
Immunodeficiency-22 (IMD22) is an autosomal recessive disorder characterized by the onset of recurrent bacterial, viral, and fungal respiratory, gastrointestinal, and skin infections in infancy or early childhood. Immunologic workup shows severe T-cell lymphopenia, particularly affecting the CD4+ subset, and impaired proximal TCR intracellular signaling and activation. Although NK cells and B cells are normal, some patients may have hypogammaglobulinemia secondary to the T-cell defect. There are variable manifestations, likely due to the severity of the particular LCK mutation: patients may develop prominent skin lesions resembling epidermodysplasia verruciformis, gastrointestinal inflammation, and virus-induced malignancy. The disease can be fatal in childhood, but hematopoietic stem cell transplant (HSCT) may be curative (Hauck et al., 2012; Li et al., 2016; Keller et al., 2023).
Immunodeficiency 23
MedGen UID:
862808
Concept ID:
C4014371
Disease or Syndrome
IMD23 is an autosomal recessive primary immunodeficiency syndrome characterized by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity (summary by Bjorksten and Lundmark, 1976 and Zhang et al., 2014).
Polyglucosan body myopathy type 1
MedGen UID:
863042
Concept ID:
C4014605
Disease or Syndrome
Polyglucosan body myopathy-1 (PGBM1) is an autosomal recessive disorder characterized by onset in childhood of progressive proximal muscle weakness, resulting in difficulties in ambulation. Most patients also develop progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. A small subset of patients present with severe immunodeficiency and a hyperinflammatory state in very early childhood (summary by Boisson et al., 2012 and Nilsson et al., 2013). Genetic Heterogeneity of Polyglucosan Body Myopathy See also PGBM2 (616199), caused by mutation in the GYG1 gene (603942) on chromosome 3q24.
Severe combined immunodeficiency due to CTPS1 deficiency
MedGen UID:
863054
Concept ID:
C4014617
Disease or Syndrome
IMD24 is an autosomal recessive immunodeficiency characterized by the impaired capacity of activated T and B cells to proliferate in response to antigen receptor-mediated activation. Patients have early onset of severe chronic viral infections, mostly caused by herpesviruses, including Epstein-Barr virus (EBV) and varicella zoster virus (VZV); they also suffer from recurrent encapsulated bacterial infections, a spectrum typical of a combined deficiency of adaptive immunity (CID) (summary by Martin et al., 2014).
Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency
MedGen UID:
863300
Concept ID:
C4014863
Disease or Syndrome
Immunodeficiency-27B (IMD27B) results from autosomal dominant (AD) IFNGR1 deficiency. Patients with AD IFNGR1 deficiency commonly present with recurrent, moderately severe infections with environmental mycobacteria or bacillus Calmette-Guerin (BCG). In contrast with patients with complete autosomal recessive (AR) IFNGR1 deficiency (IMD27A), cells from patients with AD IFNGR1 deficiency display residual responses to IFNG in vitro, indicating that the deficiency in IFNGR1 is partial. The clinical features of AD IFNGR1 deficiency are usually less severe than those in children with complete AR IFNGR1 deficiency, and mycobacterial infection often occurs later (mean age of 13.4 years vs 1.3 years), with patients having longer mean disease-free survival. In patients with AD IFNGR1 deficiency, M. avium tends to cause unifocal or multifocal osteomyelitis. Salmonellosis is present in about 5% of patients with AR or AD IFNGR1 deficiency, and other infections have been reported in single patients (review by Al-Muhsen and Casanova, 2008).
Immunodeficiency 36
MedGen UID:
863371
Concept ID:
C4014934
Disease or Syndrome
Immunodeficiency-36 with lymphoproliferation (IMD36) is an autosomal dominant primary immunodeficiency with a highly heterogeneous clinical phenotype, characterized primarily by recurrent respiratory tract infections, lymphoproliferation, and antibody deficiency. Other features include growth retardation, mild neurodevelopmental delay, and autoimmunity. The major complication is development of B-cell lymphoma (Elkaim et al., 2016).
Immunodeficiency 37
MedGen UID:
863632
Concept ID:
C4015195
Disease or Syndrome
Any primary immunodeficiency disease in which the cause of the disease is a mutation in the BCL10 gene.
Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
MedGen UID:
863651
Concept ID:
C4015214
Disease or Syndrome
Immune dysregulation with autoimmunity, immunodeficiency, and lymphoproliferation (IDAIL) is an autosomal dominant complex immune disorder with highly variable presentation and clinical manifestations. Prominent features include recurrent infections often associated with hypogammaglobulinemia, autoimmune features such as autoimmune cytopenias, and abnormal lymphocytic infiltration of nonlymphoid organs, including the lungs, brain, and gastrointestinal tract, resulting in enteropathy. Laboratory studies often show lymphopenia and abnormal T and B cell subsets. The variable features are a result of impaired function of Treg cells, which play a role in immune homeostasis (summary by Kuehn et al., 2014; Schwab et al., 2018, and Lopez-Nevado et al., 2021). The disorder shows overlapping features with autoimmune lymphoproliferative syndrome (ALPS); for a general description and a discussion of genetic heterogeneity of ALPS, see 601859.
Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency
MedGen UID:
863730
Concept ID:
C4015293
Disease or Syndrome
IMD38 predisposes individuals to severe clinical disease upon infection with weakly virulent mycobacteria, including Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccines (Bogunovic et al., 2012). Patients do not experience severe disease in response to viral infection. Affected individuals have intracranial calcification (Zhang et al., 2015).
Immunodeficiency 32B
MedGen UID:
865178
Concept ID:
C4016741
Disease or Syndrome
Immunodeficiency-32B is an autosomal recessive primary immunodeficiency characterized by recurrent infections resulting from variable defects in immune cell development or function, including monocytes, dendritic cells, and natural killer (NK) cells. Patients have particular susceptibility to viral disease (summary by Mace et al., 2017).
Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome
MedGen UID:
906646
Concept ID:
C4225222
Disease or Syndrome
Takenouchi-Kosaki syndrome is a highly heterogeneous autosomal dominant complex congenital developmental disorder affecting multiple organ systems. The core phenotype includes delayed psychomotor development with variable intellectual disability, dysmorphic facial features, and cardiac, genitourinary, and hematologic or lymphatic defects, including thrombocytopenia and lymphedema. Additional features may include abnormalities on brain imaging, skeletal anomalies, and recurrent infections. Some patients have a milder disease course reminiscent of Noonan syndrome (see, e.g., NS1, 163950) (summary by Martinelli et al., 2018).
Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome
MedGen UID:
895574
Concept ID:
C4225276
Disease or Syndrome
Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities (NEDHSB) is an autosomal recessive disorder characterized by severe neurologic impairment including impaired intellectual development, epilepsy, microcephaly, abnormal muscle tone, and sensorineural hearing loss. Most affected individuals are nonambulatory, cannot sit unassisted, and have no speech development. More variable features include feeding difficulties, poor growth, cortical visual impairment, spasticity, scoliosis, immunodeficiency, and thrombocytopenia (Tanaka et al., 2015).
Short stature, microcephaly, and endocrine dysfunction
MedGen UID:
895448
Concept ID:
C4225288
Disease or Syndrome
In patients with SSMED, short stature and microcephaly are apparent at birth, and there is progressive postnatal growth failure. Endocrine dysfunction, including hypergonadotropic hypogonadism, multinodular goiter, and diabetes mellitus, is present in affected adults. Progressive ataxia has been reported in some patients, with onset ranging from the second to fifth decade of life. In addition, a few patients have developed tumors, suggesting that there may be a predisposition to tumorigenesis. In contrast to syndromes involving defects in other components of the nonhomologous end-joining (NHEJ) complex (see, e.g., 606593), no clinically overt immunodeficiency has been observed in SSMED, although laboratory analysis has revealed lymphopenia or borderline leukopenia in some patients (Murray et al., 2015; Bee et al., 2015; de Bruin et al., 2015; Guo et al., 2015).
Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome
MedGen UID:
897984
Concept ID:
C4225351
Disease or Syndrome
White-Sutton syndrome is a neurodevelopmental disorder characterized by a wide spectrum of cognitive dysfunction, developmental delays (particularly in speech and language acquisition), hypotonia, autism spectrum disorder, and other behavioral problems. Additional features commonly reported include seizures, refractive errors and strabismus, hearing loss, sleep disturbance (particularly sleep apnea), feeding and gastrointestinal problems, mild genital abnormalities in males, and urinary tract involvement in both males and females.
Immunodeficiency 39
MedGen UID:
904167
Concept ID:
C4225358
Disease or Syndrome
Any primary immunodeficiency disease in which the cause of the disease is a mutation in the IRF7 gene.
Hermansky-Pudlak syndrome 10
MedGen UID:
934713
Concept ID:
C4310746
Disease or Syndrome
Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and, in some individuals, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. Ocular findings include reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in variable bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects occur primarily in individuals with pathogenic variants in AP3B1 and AP3D1.
Severe combined immunodeficiency due to LAT deficiency
MedGen UID:
1384124
Concept ID:
C4479588
Disease or Syndrome
IMD52 is an autosomal recessive primary immunodeficiency with variable manifestations, including severe combined immunodeficiency, hematologic autoimmune disorders, progressive lymphopenia and hypogammaglobulinemia, and lymphoproliferation with splenomegaly. Patients develop severe recurrent infections from infancy, and most die without bone marrow transplantation. The variable clinical features result from a defect in T-cell receptor signaling (summary by Keller et al., 2016 and Bacchelli et al., 2017).
Pilarowski-Bjornsson syndrome
MedGen UID:
1619150
Concept ID:
C4540131
Disease or Syndrome
Pilarowski-Bjornsson syndrome (PILBOS) is an autosomal dominant neurodevelopmental disorder characterized by delayed development, impaired intellectual development, often with autistic features, speech apraxia, and mild dysmorphic features. Some patients may have seizures. The phenotype is somewhat variable (summary by Pilarowski et al., 2018).
Immunodeficiency, developmental delay, and hypohomocysteinemia
MedGen UID:
1616061
Concept ID:
C4540293
Disease or Syndrome
IMDDHH is a multisystem disorder characterized by immunodeficiency, mildly delayed psychomotor development, poor overall growth from infancy, and hypohomocysteinemia. Additional features, such as congenital heart defects and liver involvement, are more variable (summary by Huppke et al., 2017).
Immunodeficiency-centromeric instability-facial anomalies syndrome 1
MedGen UID:
1636193
Concept ID:
C4551557
Disease or Syndrome
Immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disease characterized by facial dysmorphism, immunoglobulin deficiency, and branching of chromosomes 1, 9, and 16 after phytohemagglutinin (PHA) stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients that is explained by mutations in the DNMT3B gene in some, but not all, ICF patients (Hagleitner et al., 2008). Genetic Heterogeneity of Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome See also ICF2 (614069), caused by mutation in the ZBTB24 gene (614064) on chromosome 6q21; ICF3 (616910), caused by mutation in the CDCA7 gene (609937) on chromosome 2q31; and ICF4 (616911), caused by mutation in the HELLS gene (603946) on chromosome 10q23.
Severe combined immunodeficiency due to IKK2 deficiency
MedGen UID:
1648569
Concept ID:
C4747743
Disease or Syndrome
Immunodeficiency-15B (IMD15B) is an autosomal recessive primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinemia with relatively normal numbers of B and T cells. However, functional studies show impaired differentiation and activation of immune cells (summary by Pannicke et al., 2013).
Spondyloepimetaphyseal dysplasia, Krakow type
MedGen UID:
1648323
Concept ID:
C4748455
Disease or Syndrome
Krakow-type spondyloepimetaphyseal dysplasia is characterized by severe skeletal dysplasia, severe immunodeficiency, and developmental delay (Csukasi et al., 2018).
Trichohepatoneurodevelopmental syndrome
MedGen UID:
1648322
Concept ID:
C4748898
Disease or Syndrome
Trichohepatoneurodevelopmental syndrome is a complex multisystem disorder characterized by woolly or coarse hair, liver dysfunction, pruritus, dysmorphic features, hypotonia, and severe global developmental delay (Morimoto et al., 2018).
Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency
MedGen UID:
1684464
Concept ID:
C5193036
Disease or Syndrome
IMAGEI is an autosomal recessive disorder characterized by intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency. Patients exhibit distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency (Logan et al., 2018). An autosomal dominant form of the disorder, without immunodeficiency (IMAGE; 614732), is caused by mutation in the CDKN1C gene (600856) on chromosome 11p15.
Immunodeficiency 63 with lymphoproliferation and autoimmunity
MedGen UID:
1682943
Concept ID:
C5193126
Disease or Syndrome
Immunodeficiency-63 with lymphoproliferation and autoimmunity (IMD63) is an autosomal recessive disorder characterized by immune dysregulation. Affected individuals present in infancy with features of both abnormal activation of certain immune signaling pathways, resulting in lymphoid proliferation, dermatitis, enteropathy, and hypergammaglobulinemia, as well as features of immunodeficiency, such as recurrent infections and increased susceptibility to viral infections, especially CMV. Laboratory studies show increased NK cells that show impaired differentiation, as well as abnormal T cell populations or responses. Some patients may die in childhood; hematopoietic bone marrow transplantation is curative (summary by Zhang et al., 2019).
X-linked lymphoproliferative disease due to SH2D1A deficiency
MedGen UID:
1770239
Concept ID:
C5399825
Disease or Syndrome
X-linked lymphoproliferative disease (XLP) has two recognizable subtypes, XLP1 and XLP2. XLP1 is characterized predominantly by one of three commonly recognized phenotypes: Inappropriate immune response to Epstein-Barr virus (EBV) infection leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis. Dysgammaglobulinemia. Lymphoproliferative disease (malignant lymphoma). XLP2 is most often characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease. HLH resulting from EBV infection is associated with an unregulated and exaggerated immune response with widespread proliferation of cytotoxic T cells, EBV-infected B cells, and macrophages. Dysgammaglobulinemia is typically hypogammaglobulinemia of one or more immunoglobulin subclasses. The malignant lymphomas are typically B-cell lymphomas, non-Hodgkin type, often extranodal, and in particular involving the intestine.
Immunodeficiency 70
MedGen UID:
1740270
Concept ID:
C5436501
Disease or Syndrome
Immunodeficiency-70 (IMD70) is an autosomal dominant immunologic disorder characterized by severe cutaneous warts on the hands, feet, and face, suggesting increased susceptibility to human papillomavirus (HPV) infection. Affected individuals may also have recurrent bacterial infections, such as sinusitis, as well as feature of autoinflammation, such as colitis, celiac disease, and retinal vasculitis. Laboratory studies show decreased CD4+ T cells and decreased CD19+ B cells; hypogammaglobulinemia has also been observed (summary by Thaventhiran et al., 2020).
Immunodeficiency 80 with or without congenital cardiomyopathy
MedGen UID:
1786417
Concept ID:
C5543344
Disease or Syndrome
Immunodeficiency-80 with or without congenital cardiomyopathy (IMD80) is an autosomal recessive immunologic disorder with variable manifestations. One patient with infantile-onset of chronic cytomegalovirus (CMV) infection associated with severely decreased NK cells has been reported. Another family with 3 affected fetuses showing restrictive cardiomyopathy and hypoplasia of the spleen and thymus has also been reported (summary by Baxley et al., 2021).
Immunodeficiency 81
MedGen UID:
1788669
Concept ID:
C5543540
Disease or Syndrome
Immunodeficiency-81 (IMD81) is an autosomal recessive complex immunologic disorder with onset of symptoms in infancy. The phenotype is highly variable and may include both immunodeficiency with recurrent infections, including bacterial and fungal infections, as well as autoimmune features, including autoimmune hemolytic anemia, pancytopenia, thrombocytopenia, and inflammatory bowel disease. Immunologic workup shows immune dysregulation with abnormalities affecting multiple immune cell lineages, including T cells, B cells, NK cells, and neutrophils, which may be decreased or increased and demonstrate functional deficits. There is a wide range of hematologic abnormalities. Affected individuals may be susceptible to severe EBV infection. The disorder is caused by a defect in intracellular immune signaling pathways (summary by Lev et al., 2021; Edwards et al., 2023).
DEGCAGS syndrome
MedGen UID:
1794177
Concept ID:
C5561967
Disease or Syndrome
DEGCAGS syndrome is an autosomal recessive syndromic neurodevelopmental disorder characterized by global developmental delay, coarse and dysmorphic facial features, and poor growth and feeding apparent from infancy. Affected individuals have variable systemic manifestations often with significant structural defects of the cardiovascular, genitourinary, gastrointestinal, and/or skeletal systems. Additional features may include sensorineural hearing loss, hypotonia, anemia or pancytopenia, and immunodeficiency with recurrent infections. Death in childhood may occur (summary by Bertoli-Avella et al., 2021).
TFRC-related combined immunodeficiency
MedGen UID:
1799556
Concept ID:
C5568133
Disease or Syndrome
A rare genetic combined T and B cell immunodeficiency characterised by life-threatening infections due to disrupted transferrin receptor 1 endocytosis, resulting in defective cellular iron transport and impaired T and B cell function. Patients present with early-onset chronic diarrhoea, severe recurrent infections and failure to thrive. Laboratory studies reveal hypo or agammaglobulinaemia, normal lymphocyte counts but decreased numbers of memory B cells, intermittent neutropenia and thrombocytopenia, and mild anaemia (resistant to iron supplementation) with low mean corpuscular volume.
Gastrointestinal defects and immunodeficiency syndrome 2
MedGen UID:
1811526
Concept ID:
C5676901
Disease or Syndrome
PI4KA-related disorder is a clinically variable disorder characterized primarily by neurologic dysfunction (limb spasticity, developmental delay, intellectual disability, seizures, ataxia, nystagmus), gastrointestinal manifestations (multiple intestinal atresia, inflammatory bowel disease), and combined immunodeficiency (leukopenia, variable immunoglobulin defects). Age of onset is typically antenatal or in early childhood; individuals can present with any combination of these features. Rare individuals present with later-onset hereditary spastic paraplegia. Brain MRI findings can include hypomyelinating leukodystrophy, cerebellar hypoplasia/atrophy, thin or dysplastic corpus callosum, and/or perisylvian polymicrogyria.
Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection
MedGen UID:
1823965
Concept ID:
C5774192
Disease or Syndrome
Immunodeficiency-107 with susceptibility to invasive Staphylococcus aureus infection (IMD107) is an autosomal dominant immunologic disorder characterized most often by the development of invasive and severe life-threatening infections with S. aureus affecting the skin and/or lungs. There is incomplete penetrance (about 30%) and variable expressivity. In some patients with heterozygous OTULIN mutations, an infectious agent is not identified, suggesting that low-grade infectious or even noninfectious triggers may play a role in development of the disease. The levels and function of immune cells appear normal; the molecular defect resides in fibroblasts and possibly other nonhematopoietic barrier cells that show increased susceptibility to the detrimental effects of the S. aureus alpha-toxin (Spaan et al., 2022).
Dyskeratosis congenita, autosomal recessive 8
MedGen UID:
1824030
Concept ID:
C5774257
Disease or Syndrome
Autosomal recessive dyskeratosis congenita-8 (DKCB8) is characterized by progressive bone marrow failure affecting all lineages apparent from infancy or early childhood. More variable features may include poor growth, mild developmental delay, immunodeficiency, and gastrointestinal manifestations, such as esophageal stricture or inflammatory bowel disease. Some patients may have mucocutaneous features, including oral leukoplakia, nail dystrophy, or pigmentary skin abnormalities, although these features may be absent. Unlike patients with other forms of DKC, those with DKCB8 do not have shortened telomeres, although there is evidence of telomere instability. Hematopoietic stem cell transplant may be curative (Kermasson et al., 2022). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550).
Hatipoglu immunodeficiency syndrome
MedGen UID:
1841075
Concept ID:
C5830439
Disease or Syndrome
Hatipoglu immunodeficiency syndrome (HATIS) is an autosomal recessive immunologic disorder characterized by childhood onset of failure to thrive, skin manifestations, pancytopenia, and susceptibility to recurrent infections (Harapas et al., 2022).

Professional guidelines

PubMed

Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJ Jr, Andrejak C, Böttger EC, Brozek J, Griffith DE, Guglielmetti L, Huitt GA, Knight SL, Leitman P, Marras TK, Olivier KN, Santin M, Stout JE, Tortoli E, van Ingen J, Wagner D, Winthrop KL
Eur Respir J 2020 Jul;56(1) Epub 2020 Jul 7 doi: 10.1183/13993003.00535-2020. PMID: 32636299Free PMC Article
Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJ Jr, Andrejak C, Böttger EC, Brozek J, Griffith DE, Guglielmetti L, Huitt GA, Knight SL, Leitman P, Marras TK, Olivier KN, Santin M, Stout JE, Tortoli E, van Ingen J, Wagner D, Winthrop KL
Clin Infect Dis 2020 Aug 14;71(4):e1-e36. doi: 10.1093/cid/ciaa241. PMID: 32628747Free PMC Article
Yazdani R, Habibi S, Sharifi L, Azizi G, Abolhassani H, Olbrich P, Aghamohammadi A
J Investig Allergol Clin Immunol 2020;30(1):14-34. Epub 2019 Feb 11 doi: 10.18176/jiaci.0388. PMID: 30741636

Recent clinical studies

Etiology

Remiker A, Bolling K, Verbsky J
Med Clin North Am 2024 Jan;108(1):107-121. Epub 2023 Jul 21 doi: 10.1016/j.mcna.2023.06.012. PMID: 37951645
Cutts L, Bakshi A, Walsh M, Parslew R, Eustace K
Pediatr Dermatol 2021 Mar;38(2):541-543. Epub 2021 Jan 29 doi: 10.1111/pde.14401. PMID: 33511666
Tavakol M, Jamee M, Azizi G, Sadri H, Bagheri Y, Zaki-Dizaji M, Mahdavi FS, Jadidi-Niaragh F, Tajfirooz S, Kamali AN, Aghamahdi F, Noorian S, Kojidi HT, Mosavian M, Matani R, Dolatshahi E, Porrostami K, Elahimehr N, Fatemi-Abhari M, Sharifi L, Arjmand R, Haghi S, Zainaldain H, Yazdani R, Shaghaghi M, Abolhassani H, Aghamohammadi A
Endocr Metab Immune Disord Drug Targets 2020;20(2):157-171. doi: 10.2174/1871530319666190828125316. PMID: 31456526
Pierangeli A, Antonelli G, Gentile G
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Hartmann K
Viruses 2012 Oct 31;4(11):2684-710. doi: 10.3390/v4112684. PMID: 23202500Free PMC Article

Diagnosis

Remiker A, Bolling K, Verbsky J
Med Clin North Am 2024 Jan;108(1):107-121. Epub 2023 Jul 21 doi: 10.1016/j.mcna.2023.06.012. PMID: 37951645
Peng XP, Caballero-Oteyza A, Grimbacher B
Annu Rev Pathol 2023 Jan 24;18:283-310. Epub 2022 Oct 20 doi: 10.1146/annurev-pathmechdis-031521-024229. PMID: 36266261
Tuano KS, Seth N, Chinen J
Ann Allergy Asthma Immunol 2021 Dec;127(6):617-626. Epub 2021 Sep 3 doi: 10.1016/j.anai.2021.08.413. PMID: 34481993
Yazdani R, Habibi S, Sharifi L, Azizi G, Abolhassani H, Olbrich P, Aghamohammadi A
J Investig Allergol Clin Immunol 2020;30(1):14-34. Epub 2019 Feb 11 doi: 10.18176/jiaci.0388. PMID: 30741636
Hartmann K
Viruses 2012 Oct 31;4(11):2684-710. doi: 10.3390/v4112684. PMID: 23202500Free PMC Article

Therapy

Lamers OAC, Smits BM, Leavis HL, de Bree GJ, Cunningham-Rundles C, Dalm VASH, Ho HE, Hurst JR, IJspeert H, Prevaes SMPJ, Robinson A, van Stigt AC, Terheggen-Lagro S, van de Ven AAJM, Warnatz K, van de Wijgert JHHM, van Montfrans J
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Ollivier C, Mulugeta YL, Ruggieri L, Saint-Raymond A, Yao L
Br J Clin Pharmacol 2019 Apr;85(4):675-679. Epub 2018 Dec 18 doi: 10.1111/bcp.13809. PMID: 30403304Free PMC Article
Dimitrova A, Murchison C, Oken B
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Rieder F, Steininger C
Clin Microbiol Infect 2014 May;20 Suppl 5(Suppl 5):95-102. Epub 2014 Jan 22 doi: 10.1111/1469-0691.12449. PMID: 24283990Free PMC Article

Prognosis

Takada H
Front Immunol 2021;12:803459. Epub 2021 Dec 13 doi: 10.3389/fimmu.2021.803459. PMID: 34966393Free PMC Article
Salzberger B, Buder F, Lampl B, Ehrenstein B, Hitzenbichler F, Holzmann T, Schmidt B, Hanses F
Infection 2021 Apr;49(2):233-239. Epub 2020 Oct 8 doi: 10.1007/s15010-020-01531-3. PMID: 33034020Free PMC Article
Facciolà A, Venanzi Rullo E, Ceccarelli M, D'Andrea F, Coco M, Micali C, Cacopardo B, Marino A, Cannavò SP, Di Rosa M, Condorelli F, Pellicanò GF, Guarneri C, Nunnari G
Dermatol Ther 2020 Jan;33(1):e13180. Epub 2019 Dec 9 doi: 10.1111/dth.13180. PMID: 31770477
Pana ZD, Roilides E, Warris A, Groll AH, Zaoutis T
J Pediatric Infect Dis Soc 2017 Sep 1;6(suppl_1):S3-S11. doi: 10.1093/jpids/pix046. PMID: 28927200Free PMC Article
Upadhyay A, Jaber BL, Madias NE
Semin Nephrol 2009 May;29(3):227-38. doi: 10.1016/j.semnephrol.2009.03.004. PMID: 19523571

Clinical prediction guides

Patel NH, Dey AK, Sorokin AV, Teklu M, Petrole R, Zhou W, Mehta NN
J Cardiovasc Comput Tomogr 2022 Jan-Feb;16(1):7-18. Epub 2021 Jun 24 doi: 10.1016/j.jcct.2021.06.003. PMID: 34226164
Song M, Liu Y, Lu Z, Luo H, Peng H, Chen P
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Recent systematic reviews

Ayano G, Demelash S, Abraha M, Tsegay L
AIDS Res Ther 2021 Apr 27;18(1):23. doi: 10.1186/s12981-021-00351-1. PMID: 33906698Free PMC Article
Hoste L, Van Paemel R, Haerynck F
Eur J Pediatr 2021 Jul;180(7):2019-2034. Epub 2021 Feb 18 doi: 10.1007/s00431-021-03993-5. PMID: 33599835Free PMC Article
Peebles K, Velloza J, Balkus JE, McClelland RS, Barnabas RV
Sex Transm Dis 2019 May;46(5):304-311. doi: 10.1097/OLQ.0000000000000972. PMID: 30624309
Abdel-Wahab N, Lopez-Olivo MA, Pinto-Patarroyo GP, Suarez-Almazor ME
Lupus 2016 Dec;25(14):1520-1531. Epub 2016 Apr 7 doi: 10.1177/0961203316640912. PMID: 27060064Free PMC Article
Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, Gonzalvez Perales JL, Bort-Marti S
Cochrane Database Syst Rev 2013 Mar 28;2013(3):CD004310. doi: 10.1002/14651858.CD004310.pub3. PMID: 23543530Free PMC Article

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