U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Autoimmune hemolytic anemia

MedGen UID:
1918
Concept ID:
C0002880
Disease or Syndrome
Synonyms: Acquired autoimmune hemolytic anemia; Familial auto-immune hemolytic anemia (subtype); Idiopathic autoimmune hemolytic anemia; Immuno-hemolytic anemia
SNOMED CT: Autoimmune hemolytic anemia (413603009)
Modes of inheritance:
Non-Mendelian inheritance
MedGen UID:
109109
Concept ID:
C0600599
Genetic Function
Source: Orphanet
A mode of inheritance that depends on genetic determinants in more than one gene.
 
HPO: HP:0001890
Monarch Initiative: MONDO:0020108
OMIM®: 205700
Orphanet: ORPHA98375

Definition

An autoimmune form of hemolytic anemia. [from HPO]

Clinical features

From HPO
Autoimmune hemolytic anemia
MedGen UID:
1918
Concept ID:
C0002880
Disease or Syndrome
An autoimmune form of hemolytic anemia.
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding

Conditions with this feature

Autoimmune hemolytic anemia
MedGen UID:
1918
Concept ID:
C0002880
Disease or Syndrome
An autoimmune form of hemolytic anemia.
Wiskott-Aldrich syndrome
MedGen UID:
21921
Concept ID:
C0043194
Disease or Syndrome
The WAS-related disorders, which include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked congenital neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes caused by pathogenic variants in WAS. WAS-related disorders usually present in infancy. Affected males have thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; eczema; and recurrent bacterial and viral infections, particularly of the ear. At least 40% of those who survive the early complications develop one or more autoimmune conditions including hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, rheumatoid arthritis, vasculitis, and immune-mediated damage to the kidneys and liver. Individuals with a WAS-related disorder, particularly those who have been exposed to Epstein-Barr virus (EBV), are at increased risk of developing lymphomas, which often occur in unusual, extranodal locations including the brain, lung, or gastrointestinal tract. Males with XLT have thrombocytopenia with small platelets; other complications of Wiskott-Aldrich syndrome, including eczema and immune dysfunction, are usually mild or absent. Males with XLN have congenital neutropenia, myeloid dysplasia, and lymphoid cell abnormalities.
Purine-nucleoside phosphorylase deficiency
MedGen UID:
75653
Concept ID:
C0268125
Disease or Syndrome
Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disorder characterized mainly by decreased T-cell function. Some patients also have neurologic impairment (review by Aust et al., 1992).
Microcephaly, normal intelligence and immunodeficiency
MedGen UID:
140771
Concept ID:
C0398791
Disease or Syndrome
Nijmegen breakage syndrome (NBS) is characterized by progressive microcephaly, early growth deficiency that improves with age, recurrent respiratory infections, an increased risk for malignancy (primarily lymphoma), and premature ovarian failure in females. Developmental milestones are attained at the usual time during the first year; however, borderline delays in development and hyperactivity may be observed in early childhood. Intellectual abilities tend to decline over time. Recurrent pneumonia and bronchitis may result in respiratory failure and early death. Other reported malignancies include solid tumors (e.g., medulloblastoma, glioma, rhabdomyosarcoma).
Autoimmune lymphoproliferative syndrome type 1
MedGen UID:
231300
Concept ID:
C1328840
Disease or Syndrome
Autoimmune lymphoproliferative syndrome (ALPS), caused by defective lymphocyte homeostasis, is characterized by the following: Non-malignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly with or without hypersplenism) that often improves with age. Autoimmune disease, mostly directed toward blood cells. Lifelong increased risk for both Hodgkin and non-Hodgkin lymphoma. In ALPS-FAS (the most common and best-characterized type of ALPS, associated with heterozygous germline pathogenic variants in FAS), non-malignant lymphoproliferation typically manifests in the first years of life, inexplicably waxes and wanes, and then often decreases without treatment in the second decade of life; in many affected individuals, however, neither splenomegaly nor the overall expansion of lymphocyte subsets in peripheral blood decreases. Although autoimmunity is often not present at the time of diagnosis or at the time of the most extensive lymphoproliferation, autoantibodies can be detected before autoimmune disease manifests clinically. In ALPS-FAS caused by homozygous or compound heterozygous (biallelic) pathogenic variants in FAS, severe lymphoproliferation occurs before, at, or shortly after birth, and usually results in death at an early age. ALPS-sFAS, resulting from somatic FAS pathogenic variants in selected cell populations, notably the alpha/beta double-negative T cells (a/ß-DNT cells), appears to be similar to ALPS-FAS resulting from heterozygous germline pathogenic variants in FAS, although lower incidence of splenectomy and lower lymphocyte counts have been reported in ALPS-sFAS and no cases of lymphoma have yet been published.
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 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).
Lymphopenic hypergammaglobulinemia, antibody deficiency, autoimmune hemolytic anemia, and glomerulonephritis
MedGen UID:
340877
Concept ID:
C1855470
Disease or Syndrome
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.
Autoimmune lymphoproliferative syndrome type 2A
MedGen UID:
349065
Concept ID:
C1858968
Disease or Syndrome
Autoimmune lymphoproliferative syndrome (ALPS), caused by defective lymphocyte homeostasis, is characterized by the following: Non-malignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly with or without hypersplenism) that often improves with age. Autoimmune disease, mostly directed toward blood cells. Lifelong increased risk for both Hodgkin and non-Hodgkin lymphoma. In ALPS-FAS (the most common and best-characterized type of ALPS, associated with heterozygous germline pathogenic variants in FAS), non-malignant lymphoproliferation typically manifests in the first years of life, inexplicably waxes and wanes, and then often decreases without treatment in the second decade of life; in many affected individuals, however, neither splenomegaly nor the overall expansion of lymphocyte subsets in peripheral blood decreases. Although autoimmunity is often not present at the time of diagnosis or at the time of the most extensive lymphoproliferation, autoantibodies can be detected before autoimmune disease manifests clinically. In ALPS-FAS caused by homozygous or compound heterozygous (biallelic) pathogenic variants in FAS, severe lymphoproliferation occurs before, at, or shortly after birth, and usually results in death at an early age. ALPS-sFAS, resulting from somatic FAS pathogenic variants in selected cell populations, notably the alpha/beta double-negative T cells (a/ß-DNT cells), appears to be similar to ALPS-FAS resulting from heterozygous germline pathogenic variants in FAS, although lower incidence of splenectomy and lower lymphocyte counts have been reported in ALPS-sFAS and no cases of lymphoma have yet been published.
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
MedGen UID:
354935
Concept ID:
C1863236
Disease or Syndrome
Adenosine deaminase (ADA) deficiency is a systemic purine metabolic disorder that primarily affects lymphocyte development, viability, and function. The clinical phenotypic spectrum includes: Severe combined immunodeficiency disease (SCID), often diagnosed by age six months and usually by age 12 months; Less severe "delayed" onset combined immune deficiency (CID), usually diagnosed between age one and ten years; "Late/adult onset" CID, diagnosed in the second to fourth decades; Benign "partial ADA deficiency" (very low or absent ADA activity in erythrocytes but greater ADA activity in nucleated cells), which is compatible with normal immune function. Infants with typical early-onset ADA-deficient SCID have failure to thrive and opportunistic infections associated with marked depletion of T, B, and NK lymphocytes, and an absence of both humoral and cellular immune function. If immune function is not restored, children with ADA-deficient SCID rarely survive beyond age one to two years. Infections in delayed- and late-onset types (commonly, recurrent otitis, sinusitis, and upper respiratory) may initially be less severe than those in individuals with ADA-deficient SCID; however, by the time of diagnosis these individuals often have chronic pulmonary insufficiency and may have autoimmune phenomena (cytopenias, anti-thyroid antibodies), allergies, and elevated serum concentration of IgE. The longer the disorder goes unrecognized, the more immune function deteriorates and the more likely are chronic sequelae of recurrent infection.
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).
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).
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).
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).
TCR-alpha-beta-positive T-cell deficiency
MedGen UID:
815662
Concept ID:
C3809332
Disease or Syndrome
Immunodeficiency-7 (IMD7) is an autosomal recessive immunologic disorder characterized by onset of recurrent bacterial and viral infections in infancy or early childhood. Affected individuals may also have features of immune dysregulation, including lymphadenopathy and presence of autoantibodies. Laboratory studies show increased serum IgE, low numbers of T cells, low TCR-alpha/beta cells, and increased TCR-gamma/delta cells. The disorder often results in death in childhood, although bone marrow transplant is effective (summary by Morgan et al., 2011 and Rawat et al., 2021).
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.
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)).
STAT3-related early-onset multisystem autoimmune disease
MedGen UID:
863232
Concept ID:
C4014795
Disease or Syndrome
Infantile-onset multisystem autoimmune disease-1 is characterized by early childhood onset of a spectrum of autoimmune disorders affecting multiple organs. Common manifestations include insulin-dependent diabetes mellitus and autoimmune enteropathy, or celiac disease, and autoimmune hematologic disorders. Other features include short stature and nonspecific dermatitis. More variable features include hypothyroidism, autoimmune arthritis, and delayed puberty. Some patients may show recurrent infections. The disorder results from an inborn error of cytokine signaling (summary by Flanagan et al., 2014 and Milner et al., 2015). Genetic Heterogeneity of Infantile-Onset Multisystem Autoimmune Disease See also ADMIO2 (617006), caused by mutation in the ZAP70 gene (176947) on chromosome 2q12, and ADMIO3 (620430), caused by mutation in the CBLB gene (604491) on chromosome 3q13.
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.
Immunodeficiency, common variable, 12
MedGen UID:
906018
Concept ID:
C4225277
Disease or Syndrome
Common variable immunodeficiency-12 with autoimmunity (CVID12) is an autosomal dominant complex immunologic disorder with multisystem involvement. CVID12 is mainly a primary immunodeficiency characterized by recurrent infections and associated with hypogammaglobulinemia. Notably, about half of patients develop autoimmune features, including cytopenia, as well as generalized inflammation and lymphoproliferation manifest as lymphadenopathy or hepatosplenomegaly. A smaller percentage of affected individuals (less than 20%) develop cancer, most commonly solid tumors, including lymphoma. Age at onset and disease severity are highly variable, even within the same family. There is also incomplete penetrance, such that mutation carriers may be asymptomatic, even if they have hypogammaglobulinemia. The gene involved, NFKB1, encodes a transcription factor that regulates the expression of target genes involved in the immune system, thus defining the phenotype as a disorder of immune dysregulation (summary by Fliegauf et al., 2015; Lorenzini et al., 2020). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
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).
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).
Immunodeficiency 64
MedGen UID:
1684716
Concept ID:
C5231402
Disease or Syndrome
Immunodeficiency-64 with lymphoproliferation (IMD64) is an autosomal recessive primary immunodeficiency characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Laboratory studies show variably decreased numbers of T cells, with lesser deficiencies of B and NK cells. There is impaired T-cell proliferation and activation; functional defects in B cells and NK cells may also be observed. Patients have increased susceptibility to EBV infection and may develop lymphoproliferation or EBV-associated lymphoma. Some patients may develop features of autoimmunity (summary by Salzer et al., 2016, Mao et al., 2018, and Winter et al., 2018).
Proteasome-associated autoinflammatory syndrome 4
MedGen UID:
1780127
Concept ID:
C5543053
Disease or Syndrome
Proteasome-associated autoinflammatory syndrome-4 (PRAAS4) is an autosomal recessive immunologic disorder characterized by onset of panniculitis and erythematous skin lesions in early infancy. Additional features include hepatosplenomegaly, lymphadenopathy, fever, generalized lipodystrophy, myositis, and joint contractures, as well as delayed motor and speech development. Autoimmune features, such as hemolytic anemia, may also occur. Laboratory studies show elevation of acute phase reactants and abnormal activation of the type I interferon response. Treatment with the JAK (see 147795) inhibitor ruxolitinib may result in clinical improvement (summary by de Jesus et al., 2019). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).
Immunodeficiency 78 with autoimmunity and developmental delay
MedGen UID:
1785772
Concept ID:
C5543159
Disease or Syndrome
Immunodeficiency-78 with autoimmunity and developmental delay (IMD78) is an autosomal recessive systemic disorder characterized by onset of symptoms in early childhood. Affected individuals present with features of immune deficiency, such as recurrent sinopulmonary or skin infections, as well as autoimmunity, including autoimmune cytopenias, hemolytic anemia, and thrombocytopenia. Autoimmune hepatitis or thyroid disease and central nervous system vasculitis with stroke may also occur. There is increased susceptibility to bacterial, viral, and fungal infections. Laboratory studies show lymphopenia with advanced differentiation and premature senescence of CD8+ T cells and B cells; some patients may have hypergammaglobulinemia. The findings indicate immune dysregulation. Patients also have global developmental delay with speech delay and variable intellectual disability. Many patients die prematurely, but successful hematopoietic bone marrow transplant may be curative (summary by Lu et al., 2014 and Atallah 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).
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 98 with autoinflammation, X-linked
MedGen UID:
1805285
Concept ID:
C5676883
Disease or Syndrome
X-linked immunodeficiency-98 with autoinflammation (IMD98) is characterized by onset of recurrent infections associated with lymphoproliferation and autoinflammation in the first decade of life. Mostly males are affected; carrier females may have mild symptoms. Laboratory studies show evidence of immune dysregulation, including hypogammaglobulinemia with reduced memory B cells, skewed T-cell subsets, increased levels of proinflammatory cytokines, activated T cells and monocytes, and autoimmune cytopenias, including neutropenia (Aluri et al., 2021; Fejtkova et al., 2022).
Immunodeficiency 97 with autoinflammation
MedGen UID:
1802936
Concept ID:
C5676946
Disease or Syndrome
Immunodeficiency-97 with autoinflammation (IMD97) is an autosomal recessive complex immunologic disorder with variable features. Affected individuals present in the first decade of life with inflammatory interstitial lung disease or colitis due to abnormal tissue infiltration by activated T cells. Patients develop autoimmune cytopenias and may have lymphadenopathy; 1 reported patient had features of hemophagocytic lymphohistiocytosis (HLH; see FHL1, 267700). Some patients may have recurrent infections associated with mild lymphopenia, hypogammaglobulinemia, and NK cell dysfunction. Immunologic workup indicates signs of significant immune dysregulation with elevation of inflammatory serum markers, variable immune cell defects involving neutrophils, NK cells, and myeloid cells, and disrupted levels of T regulatory cells (Tregs). Two unrelated patients have been reported (summary by Takeda et al., 2019 and Thian et al., 2020).
Gastrointestinal defects and immunodeficiency syndrome 1
MedGen UID:
1806192
Concept ID:
C5680044
Disease or Syndrome
Gastrointestinal defects and immunodeficiency syndrome-1 (GIDID1) is characterized by multiple intestinal atresia, in which atresia occurs at various levels throughout the small and large intestines. Surgical outcomes are poor, and the condition is usually fatal within the first month of life. Some patients exhibit inflammatory bowel disease (IBD), with or without intestinal atresia, and in some cases, the intestinal features are associated with either mild or severe combined immunodeficiency (Samuels et al., 2013; Avitzur et al., 2014; Lemoine et al., 2014). Genetic Heterogeneity of GIDID See also GIDID2 (619708), caused by mutation in the PI4KA gene (600286) on chromosome 22q11.
Autoimmune disease, multisystem, infantile-onset, 3
MedGen UID:
1841236
Concept ID:
C5830600
Disease or Syndrome
Infantile-onset multisystem autoimmune disease-3 (ADMIO3) is an autosomal recessive disorder of immune dysregulation characterized by the onset of various systemic autoimmune manifestations in the first months or years of life. Features may include hypothyroidism, type 1 diabetes mellitus, systemic inflammatory manifestations (fever, hepatomegaly), and autoimmune cytopenias. Laboratory studies show normal levels of T, B, and NK cells, but CD4+ (see 186940) T cells demonstrate hyperproliferation when stimulated in vitro (Janssen et al., 2022). For a discussion of genetic heterogeneity of ADMIO, see ADMIO1 (615952).
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).
Tan-Almurshedi syndrome
MedGen UID:
1848300
Concept ID:
C5882727
Disease or Syndrome
Tan-Almurshedi syndrome (TANALS) is an autosomal recessive neurodevelopmental disorder characterized by intrauterine growth retardation, poor overall growth with short stature and microcephaly, hypotonia, global developmental delay with impaired intellectual development, poor or absent speech, spasticity, and dysmorphic facial features (Westrip et al., 2023).

Professional guidelines

PubMed

Scheckel CJ, Go RS
Hematol Oncol Clin North Am 2022 Apr;36(2):315-324. Epub 2022 Mar 11 doi: 10.1016/j.hoc.2021.12.001. PMID: 35282951
Jäger U, Barcellini W, Broome CM, Gertz MA, Hill A, Hill QA, Jilma B, Kuter DJ, Michel M, Montillo M, Röth A, Zeerleder SS, Berentsen S
Blood Rev 2020 May;41:100648. Epub 2019 Dec 5 doi: 10.1016/j.blre.2019.100648. PMID: 31839434
Jeong SH, Lee HS
Intervirology 2010;53(1):15-9. Epub 2010 Jan 5 doi: 10.1159/000252779. PMID: 20068336

Recent clinical studies

Etiology

Mulder FVM, Evers D, de Haas M, Cruijsen MJ, Bernelot Moens SJ, Barcellini W, Fattizzo B, Vos JMI
Front Immunol 2023;14:1228142. Epub 2023 Sep 18 doi: 10.3389/fimmu.2023.1228142. PMID: 37795092Free PMC Article
Barcellini W, Fattizzo B
Blood 2021 Mar 11;137(10):1283-1294. doi: 10.1182/blood.2019003808. PMID: 33512406
Barcellini W, Fattizzo B
Front Immunol 2020;11:946. Epub 2020 Jun 3 doi: 10.3389/fimmu.2020.00946. PMID: 32655543Free PMC Article
Jäger U, Barcellini W, Broome CM, Gertz MA, Hill A, Hill QA, Jilma B, Kuter DJ, Michel M, Montillo M, Röth A, Zeerleder SS, Berentsen S
Blood Rev 2020 May;41:100648. Epub 2019 Dec 5 doi: 10.1016/j.blre.2019.100648. PMID: 31839434
Broadway-Duren JB, Klaassen H
Crit Care Nurs Clin North Am 2013 Dec;25(4):411-26, v. doi: 10.1016/j.ccell.2013.09.004. PMID: 24267278

Diagnosis

Scheckel CJ, Go RS
Hematol Oncol Clin North Am 2022 Apr;36(2):315-324. Epub 2022 Mar 11 doi: 10.1016/j.hoc.2021.12.001. PMID: 35282951
Michel M
Hematol Oncol Clin North Am 2022 Apr;36(2):381-392. Epub 2022 Mar 11 doi: 10.1016/j.hoc.2021.12.004. PMID: 35282950
Barcellini W, Fattizzo B
Blood 2021 Mar 11;137(10):1283-1294. doi: 10.1182/blood.2019003808. PMID: 33512406
Barcellini W, Fattizzo B
Front Immunol 2020;11:946. Epub 2020 Jun 3 doi: 10.3389/fimmu.2020.00946. PMID: 32655543Free PMC Article
Hill A, Hill QA
Hematology Am Soc Hematol Educ Program 2018 Nov 30;2018(1):382-389. doi: 10.1182/asheducation-2018.1.382. PMID: 30504336Free PMC Article

Therapy

Berentsen S, Barcellini W
N Engl J Med 2021 Oct 7;385(15):1407-1419. doi: 10.1056/NEJMra2033982. PMID: 34614331
Barcellini W, Fattizzo B
Blood 2021 Mar 11;137(10):1283-1294. doi: 10.1182/blood.2019003808. PMID: 33512406
Jäger U, Barcellini W, Broome CM, Gertz MA, Hill A, Hill QA, Jilma B, Kuter DJ, Michel M, Montillo M, Röth A, Zeerleder SS, Berentsen S
Blood Rev 2020 May;41:100648. Epub 2019 Dec 5 doi: 10.1016/j.blre.2019.100648. PMID: 31839434
Brodsky RA
N Engl J Med 2019 Aug 15;381(7):647-654. doi: 10.1056/NEJMcp1900554. PMID: 31412178
Hill A, Hill QA
Hematology Am Soc Hematol Educ Program 2018 Nov 30;2018(1):382-389. doi: 10.1182/asheducation-2018.1.382. PMID: 30504336Free PMC Article

Prognosis

Mulder FVM, Evers D, de Haas M, Cruijsen MJ, Bernelot Moens SJ, Barcellini W, Fattizzo B, Vos JMI
Front Immunol 2023;14:1228142. Epub 2023 Sep 18 doi: 10.3389/fimmu.2023.1228142. PMID: 37795092Free PMC Article
Hwang SR, Saliba AN, Wolanskyj-Spinner AP
Hematol Oncol Clin North Am 2022 Apr;36(2):365-380. doi: 10.1016/j.hoc.2021.11.002. PMID: 35339260
Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT
Ann Rheum Dis 2021 Jan;80(1):14-25. Epub 2020 Oct 13 doi: 10.1136/annrheumdis-2020-218272. PMID: 33051219
Barcellini W, Fattizzo B
Front Immunol 2020;11:946. Epub 2020 Jun 3 doi: 10.3389/fimmu.2020.00946. PMID: 32655543Free PMC Article
Barcellini W, Fattizzo B
Dis Markers 2015;2015:635670. Epub 2015 Dec 27 doi: 10.1155/2015/635670. PMID: 26819490Free PMC Article

Clinical prediction guides

Mulder FVM, Evers D, de Haas M, Cruijsen MJ, Bernelot Moens SJ, Barcellini W, Fattizzo B, Vos JMI
Front Immunol 2023;14:1228142. Epub 2023 Sep 18 doi: 10.3389/fimmu.2023.1228142. PMID: 37795092Free PMC Article
Wu Y, Liao L, Lin F
J Clin Lab Anal 2021 Dec;35(12):e24034. Epub 2021 Oct 24 doi: 10.1002/jcla.24034. PMID: 34689357Free PMC Article
Barcellini W, Fattizzo B
Front Immunol 2020;11:946. Epub 2020 Jun 3 doi: 10.3389/fimmu.2020.00946. PMID: 32655543Free PMC Article
Barcellini W, Fattizzo B
Dis Markers 2015;2015:635670. Epub 2015 Dec 27 doi: 10.1155/2015/635670. PMID: 26819490Free PMC Article
Jeong SH, Lee HS
Intervirology 2010;53(1):15-9. Epub 2010 Jan 5 doi: 10.1159/000252779. PMID: 20068336

Recent systematic reviews

Jafarzadeh A, Jafarzadeh S, Pardehshenas M, Nemati M, Mortazavi SMJ
Int J Lab Hematol 2023 Apr;45(2):145-155. Epub 2022 Oct 8 doi: 10.1111/ijlh.13978. PMID: 36208056Free PMC Article
Jacobs JW, Booth GS
Am J Clin Pathol 2022 Jun 7;157(6):844-851. doi: 10.1093/ajcp/aqab210. PMID: 34919640Free PMC Article
Kaegi C, Wuest B, Schreiner J, Steiner UC, Vultaggio A, Matucci A, Crowley C, Boyman O
Front Immunol 2019;10:1990. Epub 2019 Sep 6 doi: 10.3389/fimmu.2019.01990. PMID: 31555262Free PMC Article
Hill QA, Hill A, Berentsen S
Blood Adv 2019 Jun 25;3(12):1897-1906. doi: 10.1182/bloodadvances.2019000036. PMID: 31235526Free PMC Article
Ungprasert P, Tanratana P, Srivali N
Thromb Res 2015 Nov;136(5):1013-7. Epub 2015 Sep 6 doi: 10.1016/j.thromres.2015.09.004. PMID: 26359320

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...