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Leukocytosis

MedGen UID:
9736
Concept ID:
C0023518
Disease or Syndrome
Synonym: Leukocytoses
SNOMED CT: Leukocytosis (111583006)
 
HPO: HP:0001974

Definition

An abnormal increase in the number of leukocytes in the blood. [from HPO]

Conditions with this feature

Hb SS disease
MedGen UID:
287
Concept ID:
C0002895
Disease or Syndrome
Sickle cell disease (SCD) is characterized by intermittent vaso-occlusive events and chronic hemolytic anemia. Vaso-occlusive events result in tissue ischemia leading to acute and chronic pain as well as organ damage that can affect any organ system, including the bones, spleen, liver, brain, lungs, kidneys, and joints. Dactylitis (pain and/or swelling of the hands or feet) is often the earliest manifestation of SCD. In children, the spleen can become engorged with blood cells in a "splenic sequestration." The spleen is particularly vulnerable to infarction and the majority of individuals with SCD who are not on hydroxyurea or transfusion therapy become functionally asplenic in early childhood, increasing their risk for certain types of bacterial infections, primarily encapsulated organisms. Acute chest syndrome (ACS) is a major cause of mortality in SCD. Chronic hemolysis can result in varying degrees of anemia, jaundice, cholelithiasis, and delayed growth and sexual maturation as well as activating pathways that contribute to the pathophysiology directly. Individuals with the highest rates of hemolysis are at higher risk for pulmonary artery hypertension, priapism, and leg ulcers and may be relatively protected from vaso-occlusive pain.
Incontinentia pigmenti syndrome
MedGen UID:
7049
Concept ID:
C0021171
Disease or Syndrome
Incontinentia pigmenti (IP) is a disorder that affects the skin, hair, teeth, nails, eyes, and central nervous system; it occurs primarily in females and on occasion in males. Characteristic skin lesions evolve through four stages: I. Blistering (birth to age ~4 months). II. Wart-like rash (for several months). III. Swirling macular hyperpigmentation (age ~6 months into adulthood). IV. Linear hypopigmentation. Alopecia, hypodontia, abnormal tooth shape, and dystrophic nails are observed. Neovascularization of the retina, present in some individuals, predisposes to retinal detachment. Neurologic findings including seizures, intellectual disability, and developmental delays are occasionally seen.
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.
Acquired polycythemia vera
MedGen UID:
45996
Concept ID:
C0032463
Neoplastic Process
Polycythemia vera (PV), the most common form of primary polycythemia, is caused by somatic mutation in a single hematopoietic stem cell leading to clonal hematopoiesis. PV is a myeloproliferative disorder characterized predominantly by erythroid hyperplasia, but also by myeloid leukocytosis, thrombocytosis, and splenomegaly. Familial cases of PV are very rare and usually manifest in elderly patients (Cario, 2005). PV is distinct from the familial erythrocytoses (see, e.g., ECYT1, 133100), which are caused by inherited mutations resulting in hypersensitivity of erythroid progenitors to hormonal influences or increased levels of circulating hormones, namely erythropoietin (EPO; 133170) (Prchal, 2005).
Radial aplasia-thrombocytopenia syndrome
MedGen UID:
61235
Concept ID:
C0175703
Disease or Syndrome
Thrombocytopenia absent radius (TAR) syndrome is characterized by bilateral absence of the radii with the presence of both thumbs, and thrombocytopenia that is generally transient. Thrombocytopenia may be congenital or may develop within the first few weeks to months of life; in general, thrombocytopenic episodes decrease with age. Cow's milk allergy is common and can be associated with exacerbation of thrombocytopenia. Other anomalies of the skeleton (upper and lower limbs, ribs, and vertebrae), heart, and genitourinary system (renal anomalies and agenesis of uterus, cervix, and upper part of the vagina) can occur.
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).
Familial eosinophilia
MedGen UID:
78796
Concept ID:
C0272192
Disease or Syndrome
Familial eosinophilia is a rare autosomal dominant disorder characterized by peripheral hypereosinophilia (greater than 500 eosinophils/micro liter of blood) with or without other oragn involvement (summary by Rioux et al., 1998).
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.
Hyperimmunoglobulin D with periodic fever
MedGen UID:
140768
Concept ID:
C0398691
Disease or Syndrome
Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. Each episode of fever lasts about 3 to 6 days, and the frequency of the episodes varies among affected individuals. In childhood the fevers seem to be more frequent, occurring as often as 25 times a year, but as the individual gets older the episodes occur less often.\n\nMevalonate kinase deficiency has additional signs and symptoms, and the severity depends on the type of the condition. There are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more severe type called mevalonic aciduria (MVA).\n\nPeople with MVA have signs and symptoms of the condition at all times, not just during episodes of fever. Affected children have developmental delay, problems with movement and balance (ataxia), recurrent seizures (epilepsy), progressive problems with vision, and failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MVA typically have an unusually small, elongated head. In childhood or adolescence, affected individuals may develop eye problems such as inflammation of the eye (uveitis), a blue tint in the white part of the eye (blue sclera), an eye disorder called retinitis pigmentosa that causes vision loss, or clouding of the lens of the eye (cataracts). Affected adults may have short stature and may develop muscle weakness (myopathy) later in life. During fever episodes, people with MVA may have an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, and skin rashes. Children with MVA who are severely affected with multiple problems may live only into early childhood; mildly affected individuals may have a normal life expectancy.\n\nDuring episodes of fever, people with HIDS typically have enlargement of the lymph nodes (lymphadenopathy), abdominal pain, joint pain, diarrhea, skin rashes, and headache. Occasionally they will have painful sores called aphthous ulcers around their mouth. In females, these may also occur around the vagina. Rarely, people with HIDS develop a buildup of protein deposits (amyloidosis) in the kidneys that can lead to kidney failure. Fever episodes in individuals with HIDS can be triggered by vaccinations, surgery, injury, or stress. Most people with HIDS have abnormally high levels of immune system proteins called immunoglobulin D (IgD) and immunoglobulin A (IgA) in the blood. It is unclear why some people with HIDS have high levels of IgD and IgA and some do not. Elevated levels of these immunoglobulins do not appear to cause any signs or symptoms. Individuals with HIDS do not have any signs and symptoms of the condition between fever episodes and typically have a normal life expectancy.
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.
Oculootoradial syndrome
MedGen UID:
233003
Concept ID:
C1327918
Disease or Syndrome
IVIC syndrome (IVIC) is an autosomal dominant disorder characterized by upper limb anomalies (radial ray defects, carpal bone fusion), extraocular motor disturbances, and congenital bilateral nonprogressive mixed hearing loss. More variable features include heart involvement, mild thrombocytopenia and leukocytosis (before age 50), shoulder girdle hypoplasia, imperforate anus, kidney malrotation, and rectovaginal fistula (summary by Paradisi and Arias, 2007).
Transient myeloproliferative syndrome
MedGen UID:
331782
Concept ID:
C1834582
Neoplastic Process
A unique clonal neoplastic disorder that is linked to trisomy 21, is restricted to neonatal period, and spontaneously regresses. It often has characteristics of megakaryocytic lineage and is associated with GATA1 mutations in myeloblasts.
Neutrophil immunodeficiency syndrome
MedGen UID:
374920
Concept ID:
C1842398
Disease or Syndrome
Immunodeficiency-73A with defective neutrophil chemotaxis and leukocytosis (IMD73A) is an immunologic disorder characterized by onset of recurrent infections in early infancy. Affected infants have periumbilical erythema and later develop skin abscesses and invasive infections. Laboratory studies show leukocytosis, neutrophilia, decreased TRECs, and T-cell abnormalities. Neutrophils showed decreased chemotaxis associated with actin polymerization abnormalities, as well as variably impaired oxidative responses. Hematopoietic stem cell transplant may be curative (summary by Accetta et al., 2011; review by Lougaris et al., 2020). In a review of autosomal forms of chronic granulomatous disease (see 306400 for genetic heterogeneity of CGD), Roos et al. (2021) noted that patients with RAC2 mutations may manifest CGD-like symptoms due to defects in neutrophil NADPH oxidase activity.
Thrombocytopenia 2
MedGen UID:
349976
Concept ID:
C1861185
Disease or Syndrome
ANKRD26-related thrombocytopenia is characterized by lifelong mild-to-moderate thrombocytopenia with a normal platelet size and no syndromic associations. Most individuals have normal hemostasis or a mild bleeding phenotype and do not develop severe spontaneous bleeding. Some individuals may have concomitant erythrocytosis and leukocytosis. The risk for myeloid malignancies (including myelodysplastic syndrome, acute myelogenous leukemia, and chronic myelogenous leukemia) is increased in individuals with ANKRD26 pathogenic variants.
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).
Autosomal recessive osteopetrosis 5
MedGen UID:
409627
Concept ID:
C1968603
Disease or Syndrome
Autosomal recessive osteopetrosis-5 is a form of infantile malignant osteopetrosis, characterized by defective osteoclast function resulting in decreased bone resorption and generalized osteosclerosis. Defective resorption causes development of densely sclerotic fragile bones and progressive obliteration of the marrow spaces and cranial foramina. Marrow obliteration is associated with extramedullary hematopoiesis and hepatosplenomegaly, and results in anemia and thrombocytopenia, whereas nerve entrapment accounts for progressive blindness and hearing loss. Other major manifestations include failure to thrive, pathologic fractures, and increased infection rate. Most affected children succumb to severe bone marrow failure and overwhelming infection in the first few years of life (Quarello et al., 2004).
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).
Anemia, nonspherocytic hemolytic, due to G6PD deficiency
MedGen UID:
403555
Concept ID:
C2720289
Disease or Syndrome
G6PD deficiency is the most common genetic cause of chronic and drug-, food-, or infection-induced hemolytic anemia. G6PD catalyzes the first reaction in the pentose phosphate pathway, which is the only NADPH-generation process in mature red cells; therefore, defense against oxidative damage is dependent on G6PD. Most G6PD-deficient patients are asymptomatic throughout their life, but G6PD deficiency can be life-threatening. The most common clinical manifestations of G6PD deficiency are neonatal jaundice and acute hemolytic anemia, which in most patients is triggered by an exogenous agent, e.g., primaquine or fava beans. Acute hemolysis is characterized by fatigue, back pain, anemia, and jaundice. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. The striking similarity between the areas where G6PD deficiency is common and Plasmodium falciparum malaria (see 611162) is endemic provided evidence that G6PD deficiency confers resistance against malaria (summary by Cappellini and Fiorelli, 2008).
Leukocyte adhesion deficiency 3
MedGen UID:
411605
Concept ID:
C2748536
Disease or Syndrome
Leukocyte adhesion deficiency-3 (LAD3), also known as LAD1 variant (LAD1V), is an autosomal recessive disorder characterized by LAD1 (116920)-like immune deficiency and Glanzmann thrombasthenia (GT; 273800)-like bleeding problems. LAD3 results from mutations in FERMT3, or KINDLIN3, which encodes an intracellular protein that interacts with beta-integrins in hematopoietic cells. In LAD3, the adhesive functions of integrins on both leukocytes and platelets are disrupted, most likely due to defects in activation-dependent alterations of surface integrins that enable high-avidity binding to ligands on target cells, a process termed 'inside-out signaling' (Svensson et al., 2009; Zimmerman, 2009). For a discussion of genetic heterogeneity of leukocyte adhesion deficiency, see 116920.
Juvenile idiopathic arthritis
MedGen UID:
760659
Concept ID:
C3495559
Disease or Syndrome
A rare, heterogeneous group of rheumatologic diseases characterized by arthritis which has an onset before 16 years of age, persists for more than 6 weeks, and is of unknown origin.
Proximal myopathy with extrapyramidal signs
MedGen UID:
816615
Concept ID:
C3810285
Disease or Syndrome
Myopathy with extrapyramidal signs is an autosomal recessive disorder characterized by early childhood onset of proximal muscle weakness and learning disabilities. While the muscle weakness is static, most patients develop progressive extrapyramidal signs that may become disabling (summary by Logan et al., 2014). Brain MRI in 1 patient showed congenital malformations, including polymicrogyria and cerebellar dysplasia (Wilton et al., 2020).
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 27A
MedGen UID:
860386
Concept ID:
C4011949
Disease or Syndrome
Immunodeficiency-27A (IMD27A) results from autosomal recessive (AR) IFNGR1 deficiency. Patients with complete IFNGR1 deficiency have a severe clinical phenotype characterized by early and often fatal mycobacterial infections. The disorder can thus be categorized as a form of mendelian susceptibility to mycobacterial disease (MSMD). Bacillus Calmette-Guerin (BCG) and environmental mycobacteria are the most frequent pathogens, and infection typically begins before the age of 3 years. Plasma from patients with complete AR IFNGR1 deficiency usually contains large amounts of IFNG (147570), and their cells do not respond to IFNG in vitro. In contrast, cells from patients with partial AR IFNGR1 deficiency, which is caused by a specific mutation in IFNGR1, retain residual responses to high IFNG concentrations. Patients with partial AR IFNGR1 deficiency are susceptible to BCG and environmental mycobacteria, but they have a milder clinical disease and better prognosis than patients with complete AR IFNGR1 deficiency. The clinical features of children with complete AR IFNGR1 deficiency are usually more severe than those in individuals with AD IFNGR1 deficiency (IMD27B), and mycobacterial infection often occurs earlier (mean age of 1.3 years vs 13.4 years), with patients having shorter mean disease-free survival. 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).
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.
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).
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).
Pulmonary alveolar proteinosis with hypogammaglobulinemia
MedGen UID:
1648298
Concept ID:
C4747984
Disease or Syndrome
Immunodeficiency-100 with pulmonary alveolar proteinosis and hypogammaglobulinemia (IMD100) is primarily a lung disorder characterized by onset of respiratory insufficiency due to pulmonary alveolar proteinosis (PAP) in the first months of life. Affected individuals may have normal respiratory function at birth. Development of the disorder appears to be influenced or triggered by viral infection, manifest as progressive respiratory insufficiency, confluent consolidations on lung imaging, and diffuse collection of periodic acid-Schiff (PAS)-positive material in pulmonary alveoli associated with small and nonfoamy alveolar macrophages. Patients also have hypogammaglobulinemia, leukocytosis, and splenomegaly. Many patients die of respiratory failure in infancy or early childhood; hematopoietic stem cell transplantation (HSCT) is curative. The pathogenesis may be related to abnormal function of alveolar macrophages, resulting in decreased catabolism of surfactant (summary by Cho et al., 2018). Magg et al. (2021) determined that the disorder results from a gain-of-function effect that particularly affects B cells and monocytes.
Inflammatory bowel disease, immunodeficiency, and encephalopathy
MedGen UID:
1648434
Concept ID:
C4748708
Disease or Syndrome
A rare genetic disease characterized by infantile onset of severe inflammatory bowel disease manifesting with bloody diarrhea and failure to thrive, and central nervous system disease with global developmental delay and regression, impaired speech, hypotonia, hyperreflexia, and epilepsy. Brain imaging shows global cerebral atrophy, thin corpus callosum, delayed myelination, and posterior leukoencephalopathy. Cases with recurrent infections and impaired T-cell responses to stimulation, as well as decreased T-cell subsets, have been reported.
Fibrosis, neurodegeneration, and cerebral angiomatosis
MedGen UID:
1648312
Concept ID:
C4748939
Disease or Syndrome
Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) is characterized by severe progressive cerebropulmonary symptoms, resulting in death in infancy from respiratory failure. Features include malabsorption, progressive growth failure, recurrent infections, chronic hemolytic anemia, and transient liver dysfunction. Neuropathology shows increased angiomatosis-like leptomeningeal, cortical, and superficial white matter vascularization and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration. Interstitial fibrosis and granuloma-like lesions are seen in the lungs, and there is hepatomegaly with steatosis and collagen accumulation (Uusimaa et al., 2018).
Pseudo-TORCH syndrome 3
MedGen UID:
1708513
Concept ID:
C5394391
Disease or Syndrome
Pseudo-TORCH syndrome-3 (PTORCH3) is an autosomal recessive disorder of immune dysregulation and neuroinflammation apparent from early infancy. Affected individuals have developmental delay with acute episodes of fever and multisystemic organ involvement, including coagulopathy, elevated liver enzymes, and proteinuria, often associated with thrombotic microangiopathy. Brain imaging shows progressive intracranial calcifications, white matter abnormalities, and sometimes cerebral or cerebellar atrophy. Laboratory studies show abnormal elevation of interferon (IFN)-stimulated gene (ISG) transcripts consistent with a type I interferonopathy. The phenotype resembles the sequelae of intrauterine infection, but there is usually no evidence of an infectious agent. The disorder results from defects in negative regulation of the interferon immunologic pathway. Death in early childhood is common (summary by Duncan et al., 2019 and Gruber et al., 2020). For a discussion of genetic heterogeneity of PTORCH, see PTORCH1 (251290).
Immunodeficiency 69
MedGen UID:
1735911
Concept ID:
C5436498
Disease or Syndrome
Immunodeficiency-69 (IMD69) is an autosomal recessive disorder characterized by increased susceptibility to disseminated mycobacterial infection, including after BCG (bacille Calmette-Guerin) vaccination. Affected individuals develop fever, hepatosplenomegaly, leukocytosis, and thrombocytosis during the acute infection. There appears to be normal immunologic function against other pathogens, including viruses and bacteria. Immunologic work-up shows normal parameters, but patient T and NK cells fail to produce gamma-interferon (IFNG) when stimulated in vitro (summary by Kerner et al., 2020). IMD69 is a form of mendelian susceptibility to mycobacterial disease (MSMD) (see, e.g., IMD27A; 209950).
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 14b, autosomal recessive
MedGen UID:
1787468
Concept ID:
C5543301
Disease or Syndrome
Autosomal recessive primary immunodeficiency-14B (IMD14B) is characterized by onset of recurrent infections in early childhood. Most patients have respiratory infections, but some may develop inflammatory bowel disease or osteomyelitis. Laboratory studies tend to show hypogammaglobulinemia and decreased levels of B cells. Although NK cell and T cell numbers are normal, there may be evidence of impaired immune-mediated cytotoxicity and defective T-cell function (summary by et al., 2018 and et al., 2019).
Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies
MedGen UID:
1784590
Concept ID:
C5543375
Disease or Syndrome
Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies (GKAF) is characterized by microcephaly, congenital alopecia, distinctive craniofacial features, severe congenital sensorineural hearing loss, global developmental delay, hydrocephalus, hypoplastic kidneys with renal insufficiency, genital hypoplasia, and early mortality (Ito et al., 2018).
Immunodeficiency 92
MedGen UID:
1794249
Concept ID:
C5562039
Disease or Syndrome
Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets. Hematopoietic stem cell transplantation may be curative (summary by Beaussant-Cohen et al., 2019 and Levy et al., 2021).
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.
Respiratory infections, recurrent, and failure to thrive with or without diarrhea
MedGen UID:
1824079
Concept ID:
C5774306
Disease or Syndrome
Recurrent respiratory infections and failure to thrive with or without diarrhea (RIFTD) is characterized by neonatal onset of chronic cough, episodic wheezing, recurrent lower respiratory tract infections, chronic diarrhea, and failure to thrive. Despite the resemblance to cystic fibrosis (CF; 219700), these patients have normal sweat chloride and pancreatic elastase tests (Bertoli-Avella et al., 2022).

Professional guidelines

PubMed

Tefferi A, Barbui T
Am J Hematol 2023 Sep;98(9):1465-1487. Epub 2023 Jun 26 doi: 10.1002/ajh.27002. PMID: 37357958
Tefferi A, Barbui T
Am J Hematol 2020 Dec;95(12):1599-1613. Epub 2020 Oct 23 doi: 10.1002/ajh.26008. PMID: 32974939
Jackson P, Vigiola Cruz M
Am Fam Physician 2018 Sep 15;98(6):362-367. PMID: 30215917

Recent clinical studies

Etiology

Coltoff A
Leuk Lymphoma 2023 Mar;64(3):564-572. Epub 2022 Dec 15 doi: 10.1080/10428194.2022.2156794. PMID: 36519233
Smith CJ, Kluck LA, Ruan GJ, Ashrani AA, Marshall AL, Pruthi RK, Shah MV, Wolanskyj-Spinner A, Gangat N, Litzow MR, Hogan WJ, Sridharan M, Go RS
Am J Med 2021 Jan;134(1):e31-e35. Epub 2020 Jul 16 doi: 10.1016/j.amjmed.2020.06.014. PMID: 32682870
Bazioti V, La Rose AM, Westerterp M
Curr Opin Lipidol 2018 Jun;29(3):233-239. doi: 10.1097/MOL.0000000000000511. PMID: 29601312
Murphy AJ, Tall AR
Eur Heart J 2016 Apr 7;37(14):1113-21. Epub 2016 Feb 10 doi: 10.1093/eurheartj/ehv718. PMID: 26869607Free PMC Article
Alvarado A
Ann Emerg Med 1986 May;15(5):557-64. doi: 10.1016/s0196-0644(86)80993-3. PMID: 3963537

Diagnosis

Macaron W, Sargsyan Z, Short NJ
Leuk Lymphoma 2022 Aug;63(8):1780-1791. Epub 2022 Mar 31 doi: 10.1080/10428194.2022.2056178. PMID: 35357988
Spivak JL
Curr Treat Options Oncol 2018 Mar 7;19(2):12. doi: 10.1007/s11864-018-0529-x. PMID: 29516275
Chabot-Richards DS, George TI
Int J Lab Hematol 2014 Jun;36(3):279-88. doi: 10.1111/ijlh.12212. PMID: 24750674
George TI
Hematology Am Soc Hematol Educ Program 2012;2012:475-84. doi: 10.1182/asheducation-2012.1.475. PMID: 23233622
Tefferi A, Hanson CA, Inwards DJ
Mayo Clin Proc 2005 Jul;80(7):923-36. doi: 10.4065/80.7.923. PMID: 16007898Free PMC Article

Therapy

Macaron W, Sargsyan Z, Short NJ
Leuk Lymphoma 2022 Aug;63(8):1780-1791. Epub 2022 Mar 31 doi: 10.1080/10428194.2022.2056178. PMID: 35357988
Barichello T, Generoso JS, Singer M, Dal-Pizzol F
Crit Care 2022 Jan 6;26(1):14. doi: 10.1186/s13054-021-03862-5. PMID: 34991675Free PMC Article
Miller T, Cudkowicz M, Shaw PJ, Andersen PM, Atassi N, Bucelli RC, Genge A, Glass J, Ladha S, Ludolph AL, Maragakis NJ, McDermott CJ, Pestronk A, Ravits J, Salachas F, Trudell R, Van Damme P, Zinman L, Bennett CF, Lane R, Sandrock A, Runz H, Graham D, Houshyar H, McCampbell A, Nestorov I, Chang I, McNeill M, Fanning L, Fradette S, Ferguson TA
N Engl J Med 2020 Jul 9;383(2):109-119. doi: 10.1056/NEJMoa2003715. PMID: 32640130
Chaves GS, Freitas DA, Santino TA, Nogueira PAM, Fregonezi GA, Mendonça KM
Cochrane Database Syst Rev 2019 Jan 2;1(1):CD010277. doi: 10.1002/14651858.CD010277.pub3. PMID: 30601584Free PMC Article
Tefferi A, Barbui T
Am J Hematol 2019 Jan;94(1):133-143. Epub 2018 Nov 9 doi: 10.1002/ajh.25303. PMID: 30281843

Prognosis

Haidar G, Chan BK, Cho ST, Hughes Kramer K, Nordstrom HR, Wallace NR, Stellfox ME, Holland M, Kline EG, Kozar JM, Kilaru SD, Pilewski JM, LiPuma JJ, Cooper VS, Shields RK, Van Tyne D
Transpl Infect Dis 2023 Apr;25(2):e14041. Epub 2023 Mar 2 doi: 10.1111/tid.14041. PMID: 36864824Free PMC Article
Leibovici-Weissman Y, Tau N, Yahav D
Aging Clin Exp Res 2021 Apr;33(4):1101-1112. Epub 2019 Sep 5 doi: 10.1007/s40520-019-01337-w. PMID: 31486996
DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Swords R, Collins RH, Mannis GN, Pollyea DA, Donnellan W, Fathi AT, Pigneux A, Erba HP, Prince GT, Stein AS, Uy GL, Foran JM, Traer E, Stuart RK, Arellano ML, Slack JL, Sekeres MA, Willekens C, Choe S, Wang H, Zhang V, Yen KE, Kapsalis SM, Yang H, Dai D, Fan B, Goldwasser M, Liu H, Agresta S, Wu B, Attar EC, Tallman MS, Stone RM, Kantarjian HM
N Engl J Med 2018 Jun 21;378(25):2386-2398. Epub 2018 Jun 2 doi: 10.1056/NEJMoa1716984. PMID: 29860938
Davis AS, Viera AJ, Mead MD
Am Fam Physician 2014 May 1;89(9):731-8. PMID: 24784336
Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi AM, Rodeghiero F, Randi ML, Vaidya R, Cazzola M, Rambaldi A, Gisslinger B, Pieri L, Ruggeri M, Bertozzi I, Sulai NH, Casetti I, Carobbio A, Jeryczynski G, Larson DR, Müllauer L, Pardanani A, Thiele J, Passamonti F, Barbui T
Leukemia 2013 Sep;27(9):1874-81. Epub 2013 Jun 6 doi: 10.1038/leu.2013.163. PMID: 23739289Free PMC Article

Clinical prediction guides

Palmer J
Hematology Am Soc Hematol Educ Program 2023 Dec 8;2023(1):676-681. doi: 10.1182/hematology.2023000453. PMID: 38066916Free PMC Article
Morsia E, Gangat N
Curr Hematol Malig Rep 2022 Feb;17(1):46-51. Epub 2021 Nov 13 doi: 10.1007/s11899-021-00660-2. PMID: 34773576
Tefferi A, Guglielmelli P, Lasho TL, Coltro G, Finke CM, Loscocco GG, Sordi B, Szuber N, Rotunno G, Pacilli A, Hanson CA, Ketterling RP, Pardanani A, Gangat N, Vannucchi AM
Br J Haematol 2020 Apr;189(2):291-302. Epub 2020 Jan 16 doi: 10.1111/bjh.16380. PMID: 31945802
Alvarado A
Ann Emerg Med 1986 May;15(5):557-64. doi: 10.1016/s0196-0644(86)80993-3. PMID: 3963537
Shoenfeld Y, Gurewich Y, Gallant LA, Pinkhas J
Am J Med 1981 Nov;71(5):773-8. doi: 10.1016/0002-9343(81)90363-6. PMID: 7304648

Recent systematic reviews

Paribello P, Manchia M, Zedda M, Pinna F, Carpiniello B
Medicina (Kaunas) 2021 Aug 11;57(8) doi: 10.3390/medicina57080816. PMID: 34441022Free PMC Article
Jafari M, Pormohammad A, Sheikh Neshin SA, Ghorbani S, Bose D, Alimohammadi S, Basirjafari S, Mohammadi M, Rasmussen-Ivey C, Razizadeh MH, Nouri-Vaskeh M, Zarei M
Rev Med Virol 2021 Sep;31(5):1-16. Epub 2021 Jan 2 doi: 10.1002/rmv.2208. PMID: 33387448Free PMC Article
Chaves GS, Freitas DA, Santino TA, Nogueira PAM, Fregonezi GA, Mendonça KM
Cochrane Database Syst Rev 2019 Jan 2;1(1):CD010277. doi: 10.1002/14651858.CD010277.pub3. PMID: 30601584Free PMC Article
Bauer ME, Price LK, MacEachern MP, Housey M, Langen ES, Bauer ST
J Obstet Gynaecol 2018 Feb;38(2):210-216. Epub 2017 Sep 14 doi: 10.1080/01443615.2017.1342614. PMID: 28903611
Rami Reddy SR, Cappell MS
Curr Gastroenterol Rep 2017 Jun;19(6):28. doi: 10.1007/s11894-017-0566-9. PMID: 28439845

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