Rheumatoid arthritis- MedGen UID:
- 2078
- •Concept ID:
- C0003873
- •
- Disease or Syndrome
Rheumatoid arthritis is an inflammatory disease, primarily of the joints, with autoimmune features and a complex genetic component.
Familial Mediterranean fever- MedGen UID:
- 45811
- •Concept ID:
- C0031069
- •
- Disease or Syndrome
Familial Mediterranean fever (FMF) is divided into two phenotypes: type 1 and type 2. FMF type 1 is characterized by recurrent short episodes of inflammation and serositis including fever, peritonitis, synovitis, pleuritis, and, rarely, pericarditis and meningitis. The symptoms and severity vary among affected individuals, sometimes even among members of the same family. Amyloidosis, which can lead to renal failure, is the most severe complication, if untreated. FMF type 2 is characterized by amyloidosis as the first clinical manifestation of FMF in an otherwise asymptomatic individual.
Acute febrile neutrophilic dermatosis- MedGen UID:
- 43097
- •Concept ID:
- C0085077
- •
- Disease or Syndrome
Acute febrile neutrophilic dermatosis (AFND) is an autosomal dominant autoinflammatory disorder characterized by onset of recurrent fever and dermatologic abnormalities in childhood. Laboratory studies show elevated acute-phase reactants and activation of the inflammatory response, particularly IL1B (147720). Additional more variable features may include myalgia and arthralgia (summary by Masters et al., 2016).
Familial amyloid nephropathy with urticaria AND deafness- MedGen UID:
- 120634
- •Concept ID:
- C0268390
- •
- Disease or Syndrome
Muckle-Wells syndrome (MWS) is characterized by episodic skin rash, arthralgias, and fever associated with late-onset sensorineural deafness and renal amyloidosis (Dode et al., 2002).
Acrodermatitis continua suppurativa of Hallopeau- MedGen UID:
- 581114
- •Concept ID:
- C0392439
- •
- Disease or Syndrome
A rare, genetic, chronic, recurrent, slowly progressive, epidermal disease characterized by small, sterile, pustular eruptions, involving the nails and surrounding skin of the fingers and/or toes, which coalesce and burst, leaving erythematous, atrophic skin where new pustules develop. Onychodystrophy is frequently associated and anonychia and osteolysis are reported in severe cases. Local expansion (to involve the hands, forearms and/or feet) and involvement of mucosal surfaces (e.g. conjunctiva, tongue, urethra) may be observed.
Leukocyte adhesion deficiency 1- MedGen UID:
- 98310
- •Concept ID:
- C0398738
- •
- Disease or Syndrome
Leukocyte adhesion deficiency (LAD) is an autosomal recessive disorder of neutrophil function resulting from a deficiency of the beta-2 integrin subunit of the leukocyte cell adhesion molecule. The leukocyte cell adhesion molecule is present on the surface of peripheral blood mononuclear leukocytes and granulocytes and mediates cell-cell and cell-extracellular matrix adhesion. LAD is characterized by recurrent bacterial infections; impaired pus formation and wound healing; abnormalities of a wide variety of adhesion-dependent functions of granulocytes, monocytes, and lymphocytes; and a lack of beta-2/alpha-L, beta-2/alpha-M, and beta-2/alpha-X expression.
Genetic Heterogeneity of Leukocyte Adhesion Deficiency
Also see LAD2 (266265), caused by mutation in the SLC35C1 gene (605881), and LAD3 (612840), caused by mutation in the FERMT3 gene (607901).
Chronic infantile neurological, cutaneous and articular syndrome- MedGen UID:
- 98370
- •Concept ID:
- C0409818
- •
- Disease or Syndrome
Chronic infantile neurologic cutaneous and articular syndrome (CINCA) is an early-onset, severe, chronic inflammatory disease, characterized by cutaneous symptoms, central nervous system involvement, and arthropathy (Feldmann et al., 2002).
See also familial cold autoinflammatory syndrome-1 (FCAS1, CAPS1; 120100), an allelic disorder with a less severe phenotype.
Heme oxygenase 1 deficiency- MedGen UID:
- 333882
- •Concept ID:
- C1841651
- •
- Disease or Syndrome
Heme oxygenase-1 deficiency (HMOX1D) is a rare autosomal recessive disorder with a complex clinical presentation including direct antibody negative hemolytic anemia, low bilirubin, and hyperinflammation (summary by Chau et al., 2020). Other features may include asplenia and nephritis (Radhakrishnan et al., 2011).
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome- MedGen UID:
- 346801
- •Concept ID:
- C1858361
- •
- Disease or Syndrome
A rare pleiotropic auto-inflammatory disorder of childhood, primarily affecting the joints and skin. The first affected family contained ten affected members from three generations and manifested variable expression of a pauciarticular, nonaxial, arthritis that began in childhood; pyoderma gangrenosum; and severe cystic acne in adolescence and beyond. Recurrent sterile arthritis usually occurs after minor trauma, but can also occur spontaneously. PAPA syndrome is a self-limiting disease, but it can lead to severe joint destruction. The gene responsible for the syndrome is the proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1).
Mevalonic aciduria- MedGen UID:
- 368373
- •Concept ID:
- C1959626
- •
- Disease or Syndrome
Mevalonic aciduria (MEVA), the first recognized defect in the biosynthesis of cholesterol and isoprenoids, is a consequence of a deficiency of mevalonate kinase (ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36). Mevalonic acid accumulates because of failure of conversion to 5-phosphomevalonic acid, which is catalyzed by mevalonate kinase. Mevalonic acid is synthesized from 3-hydroxy-3-methylglutaryl-CoA, a reaction catalyzed by HMG-CoA reductase (142910).
Mevalonic aciduria is characterized by dysmorphology, psychomotor retardation, progressive cerebellar ataxia, and recurrent febrile crises, usually manifesting in early infancy, accompanied by hepatosplenomegaly, lymphadenopathy, arthralgia, and skin rash. The febrile crises are similar to those observed in hyperimmunoglobulinemia D and to periodic fever syndrome (HIDS; 260920), which is also caused by mutation in the MVK gene (summary by Prietsch et al., 2003).
Familial cold autoinflammatory syndrome 2- MedGen UID:
- 435869
- •Concept ID:
- C2673198
- •
- Disease or Syndrome
Familial cold autoinflammatory syndrome-2 (FCAS2) is an autosomal dominant autoinflammatory disorder characterized by episodic and recurrent rash, urticaria, arthralgia, myalgia, and headache. In most patients, these episodes are accompanied by fever and serologic evidence of inflammation. Most, but not all, patients report exposure to cold as a trigger for the episodes. Additional features may include abdominal pain, thoracic pain, and sensorineural deafness. The age at onset is variable, ranging from the first year of life to middle age, and the severity and clinical manifestations are heterogeneous (summary by Shen et al., 2017).
For a phenotypic description and a discussion of genetic heterogeneity of familial cold autoinflammatory syndrome, see FCAS1 (120100).
Sterile multifocal osteomyelitis with periostitis and pustulosis- MedGen UID:
- 411230
- •Concept ID:
- C2748507
- •
- Disease or Syndrome
Chronic recurrent multifocal osteomyelitis-2 with periostitis and pustulosis (CRMO2) is an autosomal recessive multisystemic autoinflammatory disorder characterized by onset of symptoms in early infancy. Affected individuals present with joint swelling and pain, pustular rash, oral mucosal lesions, and fetal distress. The disorder progresses in severity to generalized severe pustulosis or ichthyosiform lesions and diffuse bone lesions. Radiographic studies show widening of the anterior rib ends, periosteal elevation along multiple long bones, multifocal osteolytic lesions, heterotopic ossification, and metaphyseal erosions of the long bones. Laboratory studies show elevation of inflammatory markers. The disorder results from unopposed activation of the IL1 inflammatory signaling pathway. Treatment with the interleukin-1 receptor antagonist anakinra may result in clinical improvement (Aksentijevich et al., 2009).
For a discussion of genetic heterogeneity of CRMO, see 609628.
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3- MedGen UID:
- 462759
- •Concept ID:
- C3151409
- •
- 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.
Lymphoproliferative syndrome 1- MedGen UID:
- 765548
- •Concept ID:
- C3552634
- •
- Disease or Syndrome
Lymphoproliferative syndrome-1 is an autosomal recessive primary immunodeficiency characterized by onset in early childhood of Epstein-Barr virus (EBV)-associated immune dysregulation, manifest as lymphoma, lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis, Hodgkin disease, and/or hypogammaglobulinemia. Autoimmune disorders, such as autoimmune hemolytic anemia or renal disease, may also occur. Patients show a high EBV viral load and decreased invariant natural killer T cells. It is unknown whether patients with ITK mutations are intrinsically susceptible to development of lymphoma or dysgammaglobulinemia in the absence of EBV infection (summary by Stepensky et al., 2011; Linka et al., 2012).
For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240).
Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD- MedGen UID:
- 816258
- •Concept ID:
- C3809928
- •
- Disease or Syndrome
Autoimmune lymphoproliferative syndrome type III is an autosomal recessive disorder of immune dysregulation. The phenotype is variable, but most patients have significant lymphadenopathy associated with variable autoimmune manifestations. Some patients may have recurrent infections. Lymphocyte accumulation results from a combination of impaired apoptosis and excessive proliferation (summary by Oliveira, 2013).
For a general description and a discussion of genetic heterogeneity of ALPS, see 601859.
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.
Disabling pansclerotic morphea of childhood- MedGen UID:
- 858243
- •Concept ID:
- C3898649
- •
- Disease or Syndrome
Disabling pansclerotic morphea of childhood is the most severe subtype of deep morphea within the spectrum of juvenile localized scleroderma. Patients affected by this systemic inflammatory disorder experience poor wound healing with rapidly progressive deep fibrosis involving the mucous membranes, dermis, subcutaneous fat, fascia, muscles, and bone, leading to contractures, musculoskeletal atrophy, and articular ankylosis. Systemic manifestations include cytopenias and hypogammaglobulinemia, but scleroderma-associated autoantibodies are usually not present. The disorder is associated with high morbidity and mortality due to squamous cell carcinoma, restrictive pulmonary disease, sepsis, and gangrene (Baghdassarian et al., 2023).
STING-associated vasculopathy with onset in infancy- MedGen UID:
- 863159
- •Concept ID:
- C4014722
- •
- Disease or Syndrome
STING-associated vasculopathy with onset in infancy is an autoinflammatory vasculopathy causing severe skin lesions, particularly affecting the face, ears, nose, and digits, and resulting in ulceration, eschar formation, necrosis, and, in some cases, amputation. Many patients have interstitial lung disease. Tissue biopsy and laboratory findings show a hyperinflammatory state, with evidence of increased beta-interferon (IFNB1; 147640) signaling (summary by Liu et al., 2014).
Periodic fever-infantile enterocolitis-autoinflammatory syndrome- MedGen UID:
- 863504
- •Concept ID:
- C4015067
- •
- Disease or Syndrome
Autoinflammation with infantile enterocolitis is an autosomal dominant disorder characterized by onset of recurrent flares of autoinflammation in early infancy. Affected individuals tend to have poor overall growth and gastrointestinal symptoms in infancy associated with laboratory evidence of activated inflammation. This initial presentation is followed by recurrent febrile episodes with splenomegaly and sometimes hematologic disturbances, arthralgias, or myalgias. The disorder results from overactivation of an arm of the immune response system (Romberg et al., 2014; Canna et al., 2014).
Infantile-onset periodic fever-panniculitis-dermatosis syndrome- MedGen UID:
- 934581
- •Concept ID:
- C4310614
- •
- Disease or Syndrome
Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) is an autosomal recessive autoinflammatory disease characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy. Additional features may include diarrhea, increased serum C-reactive protein (CRP), leukocytosis, and neutrophilia in the absence of any infection. Patients exhibit no overt primary immunodeficiency (Damgaard et al., 2016 and Zhou et al., 2016).
Autoinflammation with arthritis and dyskeratosis- MedGen UID:
- 1380109
- •Concept ID:
- C4479278
- •
- Disease or Syndrome
Autoinflammation with arthritis and dyskeratosis (AIADK) is characterized by recurrent fever, widespread skin dyskeratosis, arthritis, elevated biologic markers of inflammation, and mild autoimmunity with a high transitional B-cell level (summary by Grandemange et al., 2016).
Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease- MedGen UID:
- 1618052
- •Concept ID:
- C4540232
- •
- Disease or Syndrome
Immunodeficiency-71 with inflammatory disease and congenital thrombocytopenia (IMD71) is an autosomal recessive immunologic disorder characterized by the onset of recurrent infections and inflammatory features such as vasculitis and eczema in infancy or early childhood. Infectious agents include bacteria and viruses. Laboratory findings are variable, but usually show thrombocytopenia, sometimes with abnormal platelet morphology, increased serum IgE, IgA, or IgM, leukocytosis, decreased or increased T lymphocytes, and increased eosinophils. Detailed studies show impaired neutrophil and T-cell chemotaxis, as well as impaired T-cell activation due to defects in F-actin (see 102610) polymerization (summary by Brigida et al., 2018).
Familial cold autoinflammatory syndrome 1- MedGen UID:
- 1647324
- •Concept ID:
- C4551895
- •
- Disease or Syndrome
Cryopyrin-associated periodic syndromes (CAPS) are a group of conditions that have overlapping signs and symptoms and the same genetic cause. The group includes three conditions known as familial cold autoinflammatory syndrome type 1 (FCAS1), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID). These conditions were once thought to be distinct disorders but are now considered to be part of the same condition spectrum. FCAS1 is the least severe form of CAPS, MWS is intermediate in severity, and NOMID is the most severe form.\n\nThe signs and symptoms of CAPS affect multiple body systems. Generally, CAPS are characterized by periodic episodes of skin rash, fever, and joint pain. These episodes can be triggered by exposure to cold temperatures, fatigue, other stressors, or they may arise spontaneously. Episodes can last from a few hours to several days. These episodes typically begin in infancy or early childhood and persist throughout life.\n\nIn people with NOMID, the signs and symptoms of the condition are usually present from birth and persists throughout life. In addition to skin rash and fever, affected individuals may have joint inflammation, swelling, and joint deformities called contractures that may restrict movement. People with NOMID typically have headaches, seizures, and cognitive impairment resulting from chronic meningitis, which is inflammation of the tissue that covers and protects the brain and spinal cord (meninges). Other features of NOMID include eye problems, short stature, distinctive facial features, and kidney damage caused by amyloidosis.\n\nWhile the CAPS spectrum shares similar signs and symptoms, the individual conditions tend to have distinct patterns of features. People with FCAS1 are particularly sensitive to the cold, and exposure to cold temperatures can trigger a painful or burning rash. The rash usually affects the torso and limbs but may spread to the rest of the body. In addition to fever and joint pain, other possible symptoms include muscle aches, chills, drowsiness, eye redness, headache, and nausea.\n\nIndividuals with MWS develop the typical periodic episodes of skin rash, fever, and joint pain after cold exposure, although episodes may occur spontaneously or all the time. Additionally, they can develop progressive hearing loss in their teenage years. Other features of MWS include skin lesions or kidney damage from abnormal deposits of a protein called amyloid (amyloidosis).
Proteasome-associated autoinflammatory syndrome 1- MedGen UID:
- 1648310
- •Concept ID:
- C4746851
- •
- Disease or Syndrome
Proteasome-associated autoinflammatory syndrome-1 (PRAAS1) is an autosomal recessive disorder characterized by early childhood onset of annular erythematous plaques on the face and extremities with subsequent development of partial lipodystrophy and laboratory evidence of immune dysregulation. More variable features include recurrent fever, severe joint contractures, muscle weakness and atrophy, hepatosplenomegaly, basal ganglia calcifications, and microcytic anemia (summary by Agarwal et al., 2010; Kitamura et al., 2011; Arima et al., 2011).
This disorder encompasses Nakajo-Nishimura syndrome (NKJO); joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE). Among Japanese patients, this disorder is best described as Nakajo-Nishimura syndrome, since both Nakajo (1939) and Nishimura et al. (1950) contributed to the original phenotypic descriptions.
Genetic Heterogeneity of Proteasome-Associated Autoinflammatory Syndrome
See also PRAAS2 (618048), caused by mutation in the POMP gene (613386) on chromosome 13q12; PRAAS3 (617591), caused by mutation in the PSMB4 gene (602177) on chromosome 1q21; PRAAS4 (619183), caused by mutation in the PSMG2 gene (609702) on chromosome 18p11; PRAAS5 (619175), caused by mutation in the PSMB10 gene (176847) on chromosome 16q22; and PRAAS6 (620796), caused by mutation in the PSMB9 gene (177045) on chromosome 6p21.
Proteasome-associated autoinflammatory syndrome 2- MedGen UID:
- 1648482
- •Concept ID:
- C4747989
- •
- Disease or Syndrome
Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) is an autosomal dominant disorder with onset in early infancy. Affected individuals develop severe inflammatory neutrophilic dermatitis, autoimmunity, and variable immunodeficiency (summary by Poli et al., 2018).
For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).
Autoimmune interstitial lung disease-arthritis syndrome- MedGen UID:
- 1800821
- •Concept ID:
- C5243948
- •
- Disease or Syndrome
Autoimmune interstitial lung, joint, and kidney disease is an autosomal dominant systemic autoimmune disorder characterized by interstitial lung disease, inflammatory arthritis, and immune complex-mediated renal disease. Laboratory studies show high-titer autoantibodies. Symptoms appear in the first 2 decades of life, but there is incomplete penetrance (summary by Watkin et al., 2015).
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.
VEXAS syndrome- MedGen UID:
- 1765785
- •Concept ID:
- C5435753
- •
- Disease or Syndrome
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) is an adult-onset inflammatory disease that primarily affects males and is caused by somatic, not germline, mutations. The disorder is characterized by adult onset of rheumatologic symptoms at a mean age of 64 years. Features include recurrent fevers, pulmonary and dermatologic inflammatory manifestations, vasculitis, deep vein thrombosis, arthralgias, and ear and nose chondritis. Laboratory studies indicate hematologic abnormalities, including macrocytic anemia, as well as increased levels of acute-phase reactants; about half of patients have positive autoantibodies. Bone marrow biopsy shows degenerative vacuolization restricted to myeloid and erythroid precursor cells, as well as variable hematopoietic dyspoiesis and dysplasias. The condition does not respond to rheumatologic medications and the features may result in premature death (summary by Beck et al., 2020).
Inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessive- MedGen UID:
- 1783277
- •Concept ID:
- C5444224
- •
- Disease or Syndrome
Infantile ulcerative colitis (IBD31) is characterized by the presence of ulcers throughout the colon and rectum with normal-appearing ileum. Affected infants present with recurrent bloody diarrhea with anemia and leukocytosis, with extensive lymphoplasmocytic infiltration, cryptitis, and apoptotic crypt abcesses throughout the colon and rectum (Zhang et al., 2021). Infantile bowel disease has also been referred to as very-early-onset IBD (VEOIBD).
For a general description and discussion of genetic heterogeneity of inflammatory bowel disease, including Crohn disease (CD) and ulcerative colitis, see IBD1 (266600).
Immunodeficiency 82 with systemic inflammation- MedGen UID:
- 1781752
- •Concept ID:
- C5543581
- •
- Disease or Syndrome
Immunodeficiency-82 with systemic inflammation (IMD82) is a complex autosomal dominant immunologic disorder characterized by recurrent infections with various organisms, as well as noninfectious inflammation manifest as lymphocytic organ infiltration with gastritis, colitis, and lung, liver, CNS, or skin disease. One of the more common features is inflammation of the stomach and bowel. Most patients develop symptoms in infancy or early childhood; the severity is variable. There may be accompanying fever, elevated white blood cell count, decreased B cells, hypogammaglobulinemia, increased C-reactive protein (CRP; 123260), and a generalized hyperinflammatory state. Immunologic workup shows variable B- and T-cell abnormalities such as skewed subgroups. Patients have a propensity for the development of lymphoma, usually in adulthood. At the molecular level, the disorder results from a gain-of-function mutation that leads to constitutive and enhanced activation of the intracellular inflammatory signaling pathway. Treatment with SYK inhibitors rescued human cell abnormalities and resulted in clinical improvement in mice (Wang et al., 2021).
Combined oxidative phosphorylation deficiency 53- MedGen UID:
- 1779083
- •Concept ID:
- C5543631
- •
- Disease or Syndrome
Combined oxidative phosphorylation deficiency-53 (COXPD53) is an autosomal recessive disorder characterized by hypomyelination, microcephaly, liver dysfunction, and recurrent autoinflammation (summary by Lausberg et al., 2021).
For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Immunodeficiency 89 and autoimmunity- MedGen UID:
- 1794237
- •Concept ID:
- C5562027
- •
- Disease or Syndrome
Immunodeficiency-89 and autoimmunity (IMD89) is an autosomal recessive immune disorder characterized by adult onset of recurrent infections, allergies, microcytic anemia, and Crohn disease (see 266600) (Yang et al., 2020).
Immunodeficiency 87 and autoimmunity- MedGen UID:
- 1794280
- •Concept ID:
- C5562070
- •
- Disease or Syndrome
Immunodeficiency-87 and autoimmunity (IMD87) is an autosomal recessive immunologic disorder with wide phenotypic variation and severity. Affected individuals usually present in infancy or early childhood with increased susceptibility to infections, often Epstein-Barr virus (EBV), as well as with lymphadenopathy or autoimmune manifestations, predominantly hemolytic anemia. Laboratory studies may show low or normal lymphocyte numbers, often with skewed T-cell subset ratios. The disorder results primarily from defects in T-cell function, which causes both immunodeficiency and overall immune dysregulation (summary by Serwas et al., 2019 and Fournier et al., 2021).
Immunodeficiency 91 and hyperinflammation- MedGen UID:
- 1794283
- •Concept ID:
- C5562073
- •
- Disease or Syndrome
Immunodeficiency-91 and hyperinflammation (IMD91) is an autosomal recessive complex immunologic disorder characterized by both immunodeficiency and recurrent infections, often to viruses or mycobacteria, as well as by hyperinflammation with systemic involvement. Affected individuals present in infancy with variable features, including fever, infection, thrombocytopenia, renal or hepatic dysfunction, recurrent infections, or seizures. Most patients eventually develop hepatic or renal failure, compromised neurologic function, lymphadenopathy or hepatosplenomegaly, and multiorgan failure resulting in death. More variable features may include intermittent monocytosis, features of hemophagocytic lymphohistiocytosis (HLH), and serologic evidence of hyperinflammation. The disorder is thought to result from dysregulation of the interferon response to viral stimulation in the innate immune system (summary by Le Voyer et al., 2021; Vavassori et al., 2021).
Autoinflammatory syndrome, familial, X-linked, Behcet-like 2- MedGen UID:
- 1808082
- •Concept ID:
- C5575495
- •
- Disease or Syndrome
X-linked familial Behcet-like autoinflammatory syndrome-2 (AIFBL2) is an X-linked recessive disorder characterized by the onset of inflammatory symptoms in the first decade of life in male patients. Affected males often present with oral mucosal ulceration and skin inflammation. More variable features may include gastrointestinal ulceration, arthritis, recurrent fevers, and iron deficiency anemia. Laboratory studies are consistent with immune dysregulation manifest as increased inflammatory markers and variable immune cell abnormalities, such as decreased NK cells and low memory B cells. One patient presented with recurrent infections and immunodeficiency in addition to autoinflammation. The disorder results from a defect in ELF4, which normally acts as a negative regulator of inflammatory disease. Symptoms may respond to blockade of IL1 (see 147760) or TNFA (191160) (summary by Tyler et al., 2021 and Sun et al., 2022).
For a discussion of genetic heterogeneity of AIFBL, see AIFBL1 (616744).
Immunodeficiency 94 with autoinflammation and dysmorphic facies- MedGen UID:
- 1802872
- •Concept ID:
- C5676918
- •
- Disease or Syndrome
Immunodeficiency-94 with autoinflammation and dysmorphic facies (IMD94) is a systemic immunologic disorder with onset in early infancy. Primary features include lymphadenopathy, autoinflammation, immunodeficiency with hypogammaglobulinemia, and dysmorphic facial features. Intellectual development is normal and serum IgE is not elevated. The disease results from constitutive activation of the IL6 signaling cascade, resulting in immune dysregulation and a hyperinflammatory state (summary by Materna-Kiryluk et al., 2021).
C1Q deficiency 2- MedGen UID:
- 1841058
- •Concept ID:
- C5830422
- •
- Disease or Syndrome
C1q deficiency (C1QD) is a rare autosomal recessive disorder characterized by recurrent skin lesions, chronic infections, and an increased risk of autoimmune diseases, particularly systemic lupus erythematosus (SLE; see 152700) or SLE-like diseases. It has also been associated with chronic glomerulonephritis and renal failure. C1q deficiency presents in 2 different forms, absent C1q protein or presence of a dysfunctional molecule (summary by Topaloglu et al., 1996 and Vassallo et al., 2007).
For a discussion of genetic heterogeneity of C1q deficiency, see 613652.
Autoinflammatory disease, systemic, with vasculitis- MedGen UID:
- 1841161
- •Concept ID:
- C5830525
- •
- Disease or Syndrome
Systemic autoinflammatory disease with vasculitis (SAIDV) is an autosomal dominant disorder that manifests soon after birth with features such as purpuric skin rash, fever, hepatosplenomegaly, and elevated C-reactive protein (CRP; 123260). Laboratory studies may show leukocytosis, thrombocytopenia, and autoantibodies. A subset of patients develop progressive liver involvement that may result in fibrosis. Other systemic features, such as periorbital edema, conjunctivitis, infections, abdominal pain, and arthralgia are usually observed. Mutations occur de novo. De Jesus et al. (2023) referred to this disorder as LAVLI (LYN kinase-associated vasculopathy and liver fibrosis).
Immunodeficiency 113 with autoimmunity and autoinflammation- MedGen UID:
- 1851770
- •Concept ID:
- C5882711
- •
- Disease or Syndrome
Immunodeficiency-113 with autoimmunity and autoinflammation (IMD113) is an autosomal recessive complex immunologic disorder with onset of symptoms in infancy. Affected individuals have recurrent infections and usually show features of autoimmunity and autoinflammation, such as hemolytic anemia, thrombocytopenia, hepatosplenomegaly, leukocytosis, neutrophilia, and elevated acute phase reactants. More variable systemic features may include celiac disease or enteropathy, ileus, nephropathy, eczema, and dermatomyositis. Additional features include facial dysmorphism, scoliosis, and poor wound healing. One patient with neurodevelopmental abnormalities has been reported. The disorder results from dysregulation of the actin cytoskeleton that affects certain cell lineages (Nunes-Santos et al., 2023).
Immunodeficiency 115 with autoinflammation- MedGen UID:
- 1847791
- •Concept ID:
- C5882724
- •
- Disease or Syndrome
Immunodeficiency-115 with autoinflammation (IMD115) is an autosomal recessive disorder characterized by the onset of symptoms of immune dysregulation in early infancy. Affected individuals have immunodeficiency with recurrent bacterial, viral, and fungal infections, as well as autoinflammatory features, including arthritis and dermatitis. Some patients may have more systemic involvement, such as myopathy, gastrointestinal abnormalities, and anemia. Laboratory studies show variable B-cell and T-cell defects, sometimes with defective antibody responses and hypogammaglobulinemia (Boisson et al., 2015; Oda et al., 2019).