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Fever

MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Synonyms: Fevers; Pyrexia; Pyrexias
SNOMED CT: Has a temperature (50177009); Temperature raised (50177009); Increased body temperature (50177009); Fever (386661006); Pyrexial (386661006); Pyrexia (386661006); Febrile (386661006); Temperature elevated (50177009); Body temperature above reference range (50177009); High body temperature (50177009)
 
HPO: HP:0001945

Definition

Body temperature elevated above the normal range. [from HPO]

Conditions with this feature

Primary myelofibrosis
MedGen UID:
7929
Concept ID:
C0001815
Neoplastic Process
Primary myelofibrosis is a condition characterized by the buildup of scar tissue (fibrosis) in the bone marrow, the tissue that produces blood cells. Because of the fibrosis, the bone marrow is unable to make enough normal blood cells. The shortage of blood cells causes many of the signs and symptoms of primary myelofibrosis.\n\nInitially, most people with primary myelofibrosis have no signs or symptoms. Eventually, fibrosis can lead to a reduction in the number of red blood cells, white blood cells, and platelets. A shortage of red blood cells (anemia) often causes extreme tiredness (fatigue) or shortness of breath. A loss of white blood cells can lead to an increased number of infections, and a reduction of platelets can cause easy bleeding or bruising.\n\nBecause blood cell formation (hematopoiesis) in the bone marrow is disrupted, other organs such as the spleen or liver may begin to produce blood cells. This process, called extramedullary hematopoiesis, often leads to an enlarged spleen (splenomegaly) or an enlarged liver (hepatomegaly). People with splenomegaly may feel pain or fullness in the abdomen, especially below the ribs on the left side. Other common signs and symptoms of primary myelofibrosis include fever, night sweats, and bone pain.\n\nPrimary myelofibrosis is most commonly diagnosed in people aged 50 to 80 but can occur at any age.
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.
Fructose-biphosphatase deficiency
MedGen UID:
42106
Concept ID:
C0016756
Disease or Syndrome
Fructose-1,6-bisphosphatase (FBP1) deficiency is characterized by episodic acute crises of lactic acidosis and ketotic hypoglycemia, manifesting as hyperventilation, apneic spells, seizures, and/or coma. Acute crises are most common in early childhood; nearly half of affected children have hypoglycemia in the neonatal period (especially the first 4 days) resulting from deficient glycogen stores. Factors known to trigger episodes include fever, fasting, decreased oral intake, vomiting, infections, and ingestion of large amounts of fructose. In untreated individuals, symptoms worsen progressively as continued catabolism leads to multiorgan failure (especially liver, brain, and later heart). Morbidity and mortality are high. Sepsis, blindness, and Reye syndrome-like presentation have been reported. In between acute episodes, children are asymptomatic. While the majority of affected children have normal growth and psychomotor development, a few have intellectual disability, presumably due to early and prolonged hypoglycemia.
Glycogen storage disease, type II
MedGen UID:
5340
Concept ID:
C0017921
Disease or Syndrome
Pompe disease is classified by age of onset, organ involvement, severity, and rate of progression. Infantile-onset Pompe disease (IOPD; individuals with onset before age 12 months with cardiomyopathy) may be apparent in utero but more typically onset is at the median age of four months with hypotonia, generalized muscle weakness, feeding difficulties, failure to thrive, respiratory distress, and hypertrophic cardiomyopathy. Without treatment by enzyme replacement therapy (ERT), IOPD commonly results in death by age two years from progressive left ventricular outflow obstruction and respiratory insufficiency. Late-onset Pompe disease (LOPD; including: (a) individuals with onset before age 12 months without cardiomyopathy; and (b) all individuals with onset after age 12 months) is characterized by proximal muscle weakness and respiratory insufficiency; clinically significant cardiac involvement is uncommon.
Infantile cortical hyperostosis
MedGen UID:
43781
Concept ID:
C0020497
Disease or Syndrome
Caffey disease is characterized by massive subperiosteal new bone formation (usually involving the diaphyses of the long bones as well as the ribs, mandible, scapulae, and clavicles) typically associated with fever, joint swelling, and pain in children, with onset between birth and five months and spontaneous resolution by age two years. Episodes of recurrence of the manifestations of Caffey disease have been reported multiple times in individuals with the classic infantile presentation. Limited follow-up information suggests that adults who had Caffey disease in childhood may manifest joint laxity, skin hyperextensibility, hernias, short stature, and an increased risk for bone fractures and/or deformities.
Letterer-Siwe disease
MedGen UID:
7311
Concept ID:
C0023381
Disease or Syndrome
A multifocal, multisystem form of Langerhans-cell histiocytosis. There is involvement of multiple organ systems including the bones, skin, liver, spleen, and lymph nodes. Patients are usually infants presenting with fever, hepatosplenomegaly, lymphadenopathy, bone and skin lesions, and pancytopenia.
Stiff-man syndrome
MedGen UID:
39017
Concept ID:
C0085292
Disease or Syndrome
The stiff-person syndrome (SPS) is most often an adult-onset sporadic acquired disorder characterized by progressive muscle stiffness with superimposed painful muscle spasms accompanied by electromyographic evidence of continuous motor activity at rest. SPS has been associated with autoimmune disorders, diabetes mellitus, thyrotoxicosis, and hypopituitarism with adrenal insufficiency (George et al., 1984). Approximately 60% of patients with SPS have antibodies to glutamic acid decarboxylase (GAD2, or GAD65; 138275), the rate-limiting enzyme in the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), suggesting an immune-mediated pathogenesis (Folli et al., 1993). Approximately 10% of patients develop SPS as a paraneoplastic neurologic disorder associated with antibodies to amphiphysin (AMPH; 600418), an intracellular protein associated with neuronal synaptic vesicle endocytosis (Burns, 2005). See also congenital stiff-man syndrome, or hereditary hyperexplexia (149400), which is caused by mutations in subunits of the glycine receptor gene (GLRA1, 138491; GLRB, 138492). Meinck and Thompson (2002) provided a detailed review of stiff-person syndrome. They also discussed 2 possibly related conditions, progressive encephalomyelitis with rigidity (PERM), a more severe disorder with other neurologic features, and stiff-limb or stiff-leg syndrome, a focal disorder.
Hypohidrotic X-linked ectodermal dysplasia
MedGen UID:
57890
Concept ID:
C0162359
Disease or Syndrome
Hypohidrotic ectodermal dysplasia (HED) is characterized by hypotrichosis (sparseness of scalp and body hair), hypohidrosis (reduced ability to sweat), and hypodontia (congenital absence of teeth). The cardinal features of classic HED become obvious during childhood. The scalp hair is thin, lightly pigmented, and slow growing. Sweating, although present, is greatly deficient, leading to episodes of hyperthermia until the affected individual or family acquires experience with environmental modifications to control temperature. Only a few abnormally formed teeth erupt, at a later-than-average age. Physical growth and psychomotor development are otherwise within normal limits. Mild HED is characterized by mild manifestations of any or all the characteristic features.
Fatal familial insomnia
MedGen UID:
104768
Concept ID:
C0206042
Disease or Syndrome
Genetic prion disease generally manifests with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. The three major phenotypes of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Although these phenotypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset typically ranges from 50 to 60 years. The disease course ranges from a few months in gCJD and FFI to a few (up to 4, and in rare cases up to 10) years in GSS syndrome.
Cyclical neutropenia
MedGen UID:
65121
Concept ID:
C0221023
Disease or Syndrome
ELANE-related neutropenia includes congenital neutropenia and cyclic neutropenia, both of which are primary hematologic disorders characterized by recurrent fever, skin and oropharyngeal inflammation (i.e., mouth ulcers, gingivitis, sinusitis, and pharyngitis), and cervical adenopathy. Infectious complications are generally more severe in congenital neutropenia than in cyclic neutropenia. In congenital neutropenia, omphalitis immediately after birth may be the first sign; in untreated children diarrhea, pneumonia, and deep abscesses in the liver, lungs, and subcutaneous tissues are common in the first year of life. After 15 years with granulocyte colony-stimulating factor treatment, the risk of developing myelodysplasia (MDS) or acute myelogenous leukemia (AML) is approximately 15%-25%. Cyclic neutropenia is usually diagnosed within the first year of life based on approximately three-week intervals of fever and oral ulcerations and regular oscillations of blood cell counts. Cellulitis, especially perianal cellulitis, is common during neutropenic periods. Between neutropenic periods, affected individuals are generally healthy. Symptoms improve in adulthood. Cyclic neutropenia is not associated with risk of malignancy or conversion to leukemia.
Hereditary pancreatitis
MedGen UID:
116056
Concept ID:
C0238339
Disease or Syndrome
PRSS1-related hereditary pancreatitis (HP) is characterized by episodes of acute pancreatitis (AP) and recurrent acute pancreatitis (RAP: >1 episode of AP), with frequent progression to chronic pancreatitis (CP). Manifestations of acute pancreatitis can range from vague abdominal pain lasting one to three days to severe abdominal pain lasting days to weeks and requiring hospitalization.
Infantile hypophosphatasia
MedGen UID:
75677
Concept ID:
C0268412
Disease or Syndrome
Hypophosphatasia is characterized by defective mineralization of growing or remodeling bone, with or without root-intact tooth loss, in the presence of low activity of serum and bone alkaline phosphatase. Clinical features range from stillbirth without mineralized bone at the severe end to pathologic fractures of the lower extremities in later adulthood at the mild end. While the disease spectrum is a continuum, seven clinical forms of hypophosphatasia are usually recognized based on age at diagnosis and severity of features: Perinatal (severe): characterized by pulmonary insufficiency and hypercalcemia. Perinatal (benign): prenatal skeletal manifestations that slowly resolve into one of the milder forms. Infantile: onset between birth and age six months of clinical features of rickets without elevated serum alkaline phosphatase activity. Severe childhood (juvenile): variable presenting features progressing to rickets. Mild childhood: low bone mineral density for age, increased risk of fracture, and premature loss of primary teeth with intact roots. Adult: characterized by stress fractures and pseudofractures of the lower extremities in middle age, sometimes associated with early loss of adult dentition. Odontohypophosphatasia: characterized by premature exfoliation of primary teeth and/or severe dental caries without skeletal manifestations.
Tyrosinemia type I
MedGen UID:
75688
Concept ID:
C0268490
Disease or Syndrome
Untreated tyrosinemia type I usually presents either in young infants with severe liver involvement or later in the first year with liver dysfunction and renal tubular dysfunction associated with growth failure and rickets. Untreated children may have repeated, often unrecognized, neurologic crises lasting one to seven days that can include change in mental status, abdominal pain, peripheral neuropathy, and/or respiratory failure requiring mechanical ventilation. Death in the untreated child usually occurs before age ten years, typically from liver failure, neurologic crisis, or hepatocellular carcinoma. Combined treatment with nitisinone and a low-tyrosine diet has resulted in a greater than 90% survival rate, normal growth, improved liver function, prevention of cirrhosis, correction of renal tubular acidosis, and improvement in secondary rickets.
Deficiency of hydroxymethylglutaryl-CoA lyase
MedGen UID:
78692
Concept ID:
C0268601
Disease or Syndrome
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) is a rare autosomal recessive disorder with the cardinal manifestations of metabolic acidosis without ketonuria, hypoglycemia, and a characteristic pattern of elevated urinary organic acid metabolites, including 3-hydroxy-3-methylglutaric, 3-methylglutaric, and 3-hydroxyisovaleric acids. Urinary levels of 3-methylcrotonylglycine may be increased. Dicarboxylic aciduria, hepatomegaly, and hyperammonemia may also be observed. Presenting clinical signs include irritability, lethargy, coma, and vomiting (summary by Gibson et al., 1988).
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.
Anti-glomerular basement membrane disease
MedGen UID:
140788
Concept ID:
C0403529
Disease or Syndrome
A rare, fulminant small vessel vasculitis that affects the capillary beds of the kidneys and lungs and characterized by the presence of anti-glomerular basement membrane (GBM) and, in its full-blown form, anti-alveolar basement membrane (ABM) antibodies. Consequently, it may manifest as a rapidly progressive, isolated glomerulonephritis (anti-GBM nephritis) or as a pulmonary-renal syndrome with severe lung hemorrhage.
Chronic multifocal osteomyelitis
MedGen UID:
140822
Concept ID:
C0410422
Disease or Syndrome
Chronic recurrent multifocal osteomyelitis-3 (CRMO3) is an autosomal dominant autoinflammatory bone disease characterized by early childhood onset of bone pain and arthritis caused by sterile osteomyelitis. The disorder results from constitutive activation of the IL1-mediated inflammatory pathway due to loss of IL1 receptor sensitivity to its antagonist IL1RN (147679). et al. (2023) suggested the term 'Loss of IL1R1 Sensitivity to IL1RA (IL1RN)' or 'LIRSA' as a designation for this disorder. For a discussion of genetic heterogeneity of CRMO, see 609628.
Pseudodiastrophic dysplasia
MedGen UID:
140924
Concept ID:
C0432206
Disease or Syndrome
Pseudodiastrophic dysplasia (PDD) is an extremely rare and severe skeletal dysplasia associated with prenatal manifestation and early lethality. Phenotypic features include short-limbed short stature at birth, facial dysmorphism, and distinctive skeletal abnormalities including short ribs, mild to moderate platyspondyly, shortened long bones with metaphyseal flaring, elongation of the proximal and middle phalanges with subluxation of the proximal interphalangeal joints, subluxation of the elbow, and talipes equinovarus (summary by Byrne et al., 2020). Based on genetic analysis of patients with a clinical diagnosis of PDD, Byrne et al. (2020) proposed that PDD is likely not a separate genetic disorder, but rather the most severe phenotypic manifestation of skeletal dysplasia arising from defects in proteoglycan (PG) biosynthesis (see MOLECULAR GENETICS).
Subcutaneous panniculitis-like T-cell lymphoma
MedGen UID:
99306
Concept ID:
C0522624
Neoplastic Process
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon form of T-cell non-Hodgkin lymphoma in which cytotoxic CD8 (see 186910)+ T cells infiltrate adipose tissue forming subcutaneous nodules. Both children and adults can be affected, with a median age at diagnosis of 36 years and a female gender bias. Most patients have accompanying systemic features such as fever or flank pain. A subset (about 20%) of patients develop hemophagocytic lymphohistiocytosis (HLH), usually associated with CD8+ T cells rimming adipocytes in the bone marrow. An infectious agent is not identified, and the disorder is believed to result from improperly activated inflammation. Immunosuppressive therapy may be helpful; hematopoietic bone marrow transplantation is usually curative (summary by Gayden et al., 2018). For a general discussion of genetic heterogeneity of HLH, see HLH1 (267700).
Aicardi-Goutieres syndrome 1
MedGen UID:
162912
Concept ID:
C0796126
Disease or Syndrome
Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with pathogenic variants in the AGS-related genes is not yet known.
Schimke immuno-osseous dysplasia
MedGen UID:
164078
Concept ID:
C0877024
Congenital Abnormality
Schimke immunoosseous dysplasia (SIOD) is characterized by spondyloepiphyseal dysplasia (SED) resulting in short stature, nephropathy, and T-cell deficiency. Radiographic manifestations of SED include ovoid and mildly flattened vertebral bodies, small ilia with shallow dysplastic acetabular fossae, and small deformed capital femoral epiphyses. Nearly all affected individuals have progressive steroid-resistant nephropathy, usually developing within five years of the diagnosis of growth failure and terminating with end-stage renal disease. The majority of tested individuals have T-cell deficiency and an associated risk for opportunistic infection, a common cause of death. SIOD involves a spectrum that ranges from an infantile or severe early-onset form with a greater risk of death during childhood to a juvenile or milder later-onset form with likely survival into adulthood if renal disease is appropriately treated.
Upshaw-Schulman syndrome
MedGen UID:
224783
Concept ID:
C1268935
Disease or Syndrome
Hereditary thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome (USS), is a rare autosomal recessive thrombotic microangiopathy (TMA). Clinically, acute phases of TTP are defined by microangiopathic mechanical hemolytic anemia, severe thrombocytopenia, and visceral ischemia. Hereditary TTP makes up 5% of TTP cases and is caused mostly by biallelic mutation in the ADAMTS13 gene, or in very rare cases, by monoallelic ADAMTS13 mutation associated with a cluster of single-nucleotide polymorphisms (SNPs); most cases of all TTP (95%) are acquired via an autoimmune mechanism (see 188030). Hereditary TTP is more frequent among child-onset TTP compared with adult-onset TTP, and its clinical presentation is significantly different as a function of its age of onset. Child-onset TTP usually starts in the neonatal period with hematological features and severe jaundice. In contrast, almost all cases of adult-onset hereditary TTP are unmasked during the first pregnancy of a woman whose disease was silent during childhood (summary by Joly et al., 2018).
Migraine, familial hemiplegic, 1
MedGen UID:
331388
Concept ID:
C1832884
Disease or Syndrome
Familial hemiplegic migraine (FHM) falls within the category of migraine with aura. In migraine with aura (including FHM) the neurologic symptoms of aura are unequivocally localizable to the cerebral cortex or brain stem and include visual disturbance (most common), sensory loss (e.g., numbness or paresthesias of the face or an extremity), and dysphasia (difficulty with speech). FHM must include motor involvement, such as hemiparesis (weakness of an extremity). Hemiparesis occurs with at least one other symptom during FHM aura. Neurologic deficits with FHM attacks can be prolonged for hours to days and may outlast the associated migrainous headache. FHM is often earlier in onset than typical migraine, frequently beginning in the first or second decade; the frequency of attacks tends to decrease with age. Approximately 40%-50% of families with CACNA1A-FHM have cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia.
Carnitine palmitoyl transferase II deficiency, neonatal form
MedGen UID:
318896
Concept ID:
C1833518
Disease or Syndrome
Carnitine palmitoyltransferase II (CPT II) deficiency is a disorder of long-chain fatty-acid oxidation. The three clinical presentations are lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form (which is usually mild and can manifest from infancy to adulthood). While the former two are severe multisystemic diseases characterized by liver failure with hypoketotic hypoglycemia, cardiomyopathy, seizures, and early death, the latter is characterized by exercise-induced muscle pain and weakness, sometimes associated with myoglobinuria. The myopathic form of CPT II deficiency is the most common disorder of lipid metabolism affecting skeletal muscle and the most frequent cause of hereditary myoglobinuria. Males are more likely to be affected than females.
Familial hemophagocytic lymphohistiocytosis 3
MedGen UID:
332383
Concept ID:
C1837174
Disease or Syndrome
Secretion of the contents of cytolytic granules at the immunologic synapse is a highly regulated process essential for lymphocyte cytotoxicity. This process requires the rapid transfer of perforin (170280)-containing lytic granules to the target cell interface, followed by their docking and fusion with the plasma membrane. Familial hemophagocytic lymphohistiocytosis is a genetically heterogeneous condition characterized by defective cytotoxicity. For a more detailed description of FHL, see 267700.
Hyperthermia, cutaneous, with headaches and nausea
MedGen UID:
374453
Concept ID:
C1840373
Disease or Syndrome
Biotin-responsive basal ganglia disease
MedGen UID:
375289
Concept ID:
C1843807
Disease or Syndrome
Biotin-thiamine-responsive basal ganglia disease (BTBGD) may present in childhood, early infancy, or adulthood. The classic presentation of BTBGD occurs in childhood (age 3-10 years) and is characterized by recurrent subacute encephalopathy manifest as confusion, seizures, ataxia, dystonia, supranuclear facial palsy, external ophthalmoplegia, and/or dysphagia which, if left untreated, can eventually lead to coma and even death. Dystonia and cogwheel rigidity are nearly always present; hyperreflexia, ankle clonus, and Babinski responses are common. Hemiparesis or quadriparesis may be seen. Episodes are often triggered by febrile illness or mild trauma or stress. Simple partial or generalized seizures are easily controlled with anti-seizure medication. An early-infantile Leigh-like syndrome / atypical infantile spasms presentation occurs in the first three months of life with poor feeding, vomiting, acute encephalopathy, and severe lactic acidosis. An adult-onset Wernicke-like encephalopathy presentation is characterized by acute onset of status epilepticus, ataxia, nystagmus, diplopia, and ophthalmoplegia in the second decade of life. Prompt administration of biotin and thiamine early in the disease course results in partial or complete improvement within days in the childhood and adult presentations, but most with the infantile presentation have had poor outcome even after supplementation with biotin and thiamine.
Granulomatous disease, chronic, X-linked
MedGen UID:
336165
Concept ID:
C1844376
Disease or Syndrome
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis). Granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. While CGD may present anytime from infancy to late adulthood, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival.
X-linked lymphoproliferative disease due to XIAP deficiency
MedGen UID:
336848
Concept ID:
C1845076
Disease or Syndrome
X-linked lymphoproliferative disease (XLP) has two recognizable subtypes, XLP1 and XLP2. XLP1 is characterized predominantly by one of three commonly recognized phenotypes: Inappropriate immune response to Epstein-Barr virus (EBV) infection leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis. Dysgammaglobulinemia. Lymphoproliferative disease (malignant lymphoma). XLP2 is most often characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease. HLH resulting from EBV infection is associated with an unregulated and exaggerated immune response with widespread proliferation of cytotoxic T cells, EBV-infected B cells, and macrophages. Dysgammaglobulinemia is typically hypogammaglobulinemia of one or more immunoglobulin subclasses. The malignant lymphomas are typically B-cell lymphomas, non-Hodgkin type, often extranodal, and in particular involving the intestine.
Myoglobinuria, acute recurrent, autosomal recessive
MedGen UID:
340308
Concept ID:
C1849386
Disease or Syndrome
Recurrent myoglobinuria is characterized by recurrent attacks of rhabdomyolysis associated with muscle pain and weakness and followed by excretion of myoglobin in the urine. Renal failure may occasionally occur. Onset is usually in early childhood under the age of 5 years. Unlike the exercise-induced rhabdomyolyses such as McArdle syndrome (232600), carnitine palmitoyltransferase deficiency (see 255110), and the Creteil variety of phosphoglycerate kinase deficiency (311800), the attacks in recurrent myoglobinuria no relation to exercise, but are triggered by intercurrent illnesses, commonly upper respiratory tract infections (Ramesh and Gardner-Medwin, 1992). See 160010 for discussion of a possible autosomal dominant form of myoglobinuria. Severe rhabdomyolysis is a major clinical feature of anesthetic-induced malignant hyperthermia (145600), an autosomal dominant disorder.
Bartter disease type 2
MedGen UID:
343428
Concept ID:
C1855849
Disease or Syndrome
Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997). Patients with antenatal forms of Bartter syndrome typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome (see BARTS3, 607364) present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364.
Hypohidrosis with abnormal palmar dermal Ridges
MedGen UID:
340989
Concept ID:
C1855856
Disease or Syndrome
Fever, familial lifelong persistent
MedGen UID:
346443
Concept ID:
C1856788
Disease or Syndrome
Cirrhosis, familial
MedGen UID:
350049
Concept ID:
C1861556
Disease or Syndrome
Cirrhosis in which no causative agent can be identified.
Familial hemophagocytic lymphohistiocytosis 2
MedGen UID:
400366
Concept ID:
C1863727
Disease or Syndrome
Familial hemophagocytic lymphohistiocytosis-2 (FHL2) is an autosomal recessive disorder of immune dysregulation with onset in infancy or early childhood. It is characterized clinically by fever, edema, hepatosplenomegaly, and liver dysfunction. Neurologic impairment, seizures, and ataxia are frequent. Laboratory studies show pancytopenia, coagulation abnormalities, hypofibrinogenemia, and hypertriglyceridemia. There is increased production of cytokines, such as gamma-interferon (IFNG; 147570) and TNF-alpha (191160), by hyperactivation and proliferation of T cells and macrophages. Activity of cytotoxic T cells and NK cells is reduced, consistent with a defect in cellular cytotoxicity. Bone marrow, lymph nodes, spleen, and liver show features of hemophagocytosis. Chemotherapy and/or immunosuppressant therapy may result in symptomatic remission, but the disorder is fatal without bone marrow transplantation (summary by Dufourcq-Lagelouse et al., 1999, Stepp et al., 1999, and Molleran Lee et al., 2004). For a general phenotypic description and a discussion of genetic heterogeneity of FHL, see 267700.
Familial hemophagocytic lymphohistiocytosis 4
MedGen UID:
350245
Concept ID:
C1863728
Disease or Syndrome
Hemophagocytic lymphohistiocytosis is a hyperinflammatory disorder clinically diagnosed based on the fulfillment of 5 of 8 criteria, including fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low or absent natural killer (NK) cell activity, hyperferritinemia, and high soluble IL2 receptor levels (IL2R; 147730). The disorder typically presents in infancy or early childhood. Persistent remission is rarely achieved with chemo- or immunotherapy; hematopoietic stem cell transplantation is the only cure (summary by Muller et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of familial hemophagocytic lymphohistiocytosis (FHL), see 267700.
H syndrome
MedGen UID:
400532
Concept ID:
C1864445
Disease or Syndrome
The histiocytosis-lymphadenopathy plus syndrome comprises features of 4 histiocytic disorders previously thought to be distinct: Faisalabad histiocytosis (FHC), sinus histiocytosis with massive lymphadenopathy (SHML), H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome (PHID). FHC was described as an autosomal recessive disease involving joint deformities, sensorineural hearing loss, and subsequent development of generalized lymphadenopathy and swellings in the eyelids that contain histiocytes (summary by Morgan et al., 2010). SHML, or familial Rosai-Dorfman disease, was described as a rare cause of lymph node enlargement in children, consisting of chronic massive enlargement of cervical lymph nodes frequently accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Extranodal sites were involved in approximately 25% of patients, including salivary glands, orbit, eyelid, spleen, and testes. The involvement of retropharyngeal lymphoid tissue sometimes caused snoring and sleep apnea (summary by Kismet et al., 2005). H syndrome was characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism; hearing loss was also found in about half of patients, and many had short stature. PHID was characterized by predominantly antibody-negative insulin-dependent diabetes mellitus associated with pigmented hypertrichosis and variable occurrence of other features of H syndrome, with hepatosplenomegaly occurring in about half of patients (Cliffe et al., 2009). Bolze et al. (2012) noted that mutations in the SLC29A3 gene (612373) had been implicated in H syndrome, PHID, FHC, and SHML, and that some patients presented a combination of features from 2 or more of these syndromes, leading to the suggestion that these phenotypes should be grouped together as 'SLC29A3 disorder.' Bolze et al. (2012) suggested that the histologic features of the lesions seemed to be the most uniform phenotype in these patients. In addition, the immunophenotype of infiltrating cells in H syndrome patients was shown to be the same as that seen in patients with the familial form of Rosai-Dorfman disease, further supporting the relationship between these disorders (Avitan-Hersh et al., 2011; Colmenero et al., 2012).
Migraine, familial hemiplegic, 2
MedGen UID:
355962
Concept ID:
C1865322
Disease or Syndrome
Familial hemiplegic migraine (FHM) falls within the category of migraine with aura. In migraine with aura (including FHM) the neurologic symptoms of aura are unequivocally localizable to the cerebral cortex or brain stem and include visual disturbance (most common), sensory loss (e.g., numbness or paresthesias of the face or an extremity), and dysphasia (difficulty with speech). FHM must include motor involvement, such as hemiparesis (weakness of an extremity). Hemiparesis occurs with at least one other symptom during FHM aura. Neurologic deficits with FHM attacks can be prolonged for hours to days and may outlast the associated migrainous headache. FHM is often earlier in onset than typical migraine, frequently beginning in the first or second decade; the frequency of attacks tends to decrease with age. Approximately 40%-50% of families with CACNA1A-FHM have cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia.
Malignant hyperthermia, susceptibility to, 5
MedGen UID:
356151
Concept ID:
C1866077
Finding
Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances cause uncontrolled release of calcium from the sarcoplasmic reticulum and may promote entry of extracellular calcium into the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even cardiac arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some individuals with MHS will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high.
Bartter disease type 1
MedGen UID:
355727
Concept ID:
C1866495
Disease or Syndrome
Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997). Patients with antenatal forms of Bartter syndrome typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome (see BARTS3, 607364) present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364.
Griscelli syndrome type 2
MedGen UID:
357030
Concept ID:
C1868679
Disease or Syndrome
Griscelli syndrome type 2 (GS2) is an autosomal recessive disorder characterized by pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. Patients also have immunologic abnormalities with or without neurologic impairment (summary by Menasche et al., 2000). Some GS2 patients have been reported in whom central nervous system manifestations are the first presentation (Rajadhyax et al., 2007, Masri et al., 2008; Mishra et al., 2014; Lee et al., 2017). For a discussion of phenotypic and genetic heterogeneity of Griscelli syndrome, see Griscelli syndrome type 1 (GS1; 214450).
Sarcoidosis, susceptibility to, 1
MedGen UID:
394568
Concept ID:
C2697310
Finding
Any sarcoidosis in which the cause of the disease is a mutation in the HLA-DRB1 gene.
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).
Neuroblastoma, susceptibility to, 1
MedGen UID:
412713
Concept ID:
C2749485
Finding
Hemolytic uremic syndrome, atypical, susceptibility to, 1
MedGen UID:
412743
Concept ID:
C2749604
Finding
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. The onset of atypical HUS (aHUS) ranges from the neonatal period to adulthood. Genetic aHUS accounts for an estimated 60% of all aHUS. Individuals with genetic aHUS frequently experience relapse even after complete recovery following the presenting episode; 60% of genetic aHUS progresses to end-stage renal disease (ESRD).
Familial hemophagocytic lymphohistiocytosis 5
MedGen UID:
416514
Concept ID:
C2751293
Disease or Syndrome
Familial hemophagocytic lymphohistiocytosis-5 with or without microvillus inclusion disease (FHL5) is an autosomal recessive hyperinflammatory disorder characterized clinically by fever, hepatosplenomegaly, pancytopenia, coagulation abnormalities, and other laboratory findings. Some patients have neurologic symptoms due to inflammatory CNS disease. There is uncontrolled and ineffective proliferation and activation of T lymphocytes, NK cells, and macrophages that infiltrate multiple organs, including liver, spleen, lymph nodes, and the CNS. The phenotype is variable: some patients may present in early infancy with severe diarrhea, prior to the onset of typical FHL features, whereas others present later in childhood and have a more protracted course without diarrhea. The early-onset diarrhea is due to enteropathy reminiscent of microvillus inclusion disease (see MVID, 251850). The enteropathy, which often necessitates parenteral feeding, may be the most life-threatening issue even after hematopoietic stem cell transplantation (HSCT). More variable features include sensorineural hearing loss and hypogammaglobulinemia. Treatment with immunosuppressive drugs and chemotherapy can ameliorate signs and symptoms of FHL in some patients, but the only curative therapy for FHL is HSCT. HSCT is not curative for enteropathy associated with the disorder, despite hematologic and immunologic reconstitution (summary by Meeths et al., 2010; Pagel et al., 2012; Stepensky et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of familial hemophagocytic lymphohistiocytosis (FHL, HLH), see 267700.
Malignant hyperthermia, susceptibility to, 2
MedGen UID:
419301
Concept ID:
C2930981
Finding
Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances cause uncontrolled release of calcium from the sarcoplasmic reticulum and may promote entry of extracellular calcium into the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even cardiac arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some individuals with MHS will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high.
Malignant hyperthermia, susceptibility to, 3
MedGen UID:
418956
Concept ID:
C2930982
Finding
Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances cause uncontrolled release of calcium from the sarcoplasmic reticulum and may promote entry of extracellular calcium into the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even cardiac arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some individuals with MHS will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high.
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency
MedGen UID:
424833
Concept ID:
C2936858
Congenital Abnormality
21-hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), a family of autosomal recessive disorders involving impaired synthesis of cortisol from cholesterol by the adrenal cortex. In 21-OHD CAH, excessive adrenal androgen biosynthesis results in virilization in all individuals and salt wasting in some individuals. A classic form with severe enzyme deficiency and prenatal onset of virilization is distinguished from a non-classic form with mild enzyme deficiency and postnatal onset. The classic form is further divided into the simple virilizing form (~25% of affected individuals) and the salt-wasting form, in which aldosterone production is inadequate (=75% of individuals). Newborns with salt-wasting 21-OHD CAH are at risk for life-threatening salt-wasting crises. Individuals with the non-classic form of 21-OHD CAH present postnatally with signs of hyperandrogenism; females with the non-classic form are not virilized at birth.
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).
Encephalopathy, acute, infection-induced, susceptibility to, 4
MedGen UID:
481790
Concept ID:
C3280160
Finding
Acute encephalopathy is a severe neurologic complication of an infection that usually occurs in children. It is characterized by a high-grade fever accompanied within 12 to 48 hours by febrile convulsions, often leading to coma, multiple-organ failure, brain edema, and high morbidity and mortality. The infections are usually viral, particularly influenza, although other viruses and even mycoplasma have been found to cause the disorder (summary by Chen et al., 2005; Shinohara et al., 2011). For a discussion of genetic heterogeneity of susceptibility to acute infection-induced encephalopathy, see 610551.
Granulomatosis with polyangiitis
MedGen UID:
811223
Concept ID:
C3495801
Disease or Syndrome
Granulomatosis with polyangiitis, formerly termed Wegener granulomatosis, is a systemic disease with a complex genetic background. It is characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tract, glomerulonephritis, vasculitis, and the presence of antineutrophil cytoplasmatic autoantibodies (ANCAs) in patient sera. These ANCAs are antibodies to a defined target antigen, proteinase-3 (PR3, PRTN3; 177020), which is present within primary azurophil granules of neutrophils (PMNs) and lysozymes of monocytes. On cytokine priming of PMNs, PR3 translocates to the cell surface, where PR3-ANCAs can interact with their antigens and activate PMNs. PMNs from patients with active GPA express PR3 on their surface, produce respiratory burst, and release proteolytic enzymes after activation with PR3-ANCAs. The consequence is a self-sustaining inflammatory process (Jagiello et al., 2004).
Hereditary sensory and autonomic neuropathy type 6
MedGen UID:
761278
Concept ID:
C3539003
Disease or Syndrome
Hereditary sensory and autonomic neuropathy type VI (HSAN6) is a severe autosomal recessive disorder characterized by neonatal hypotonia, respiratory and feeding difficulties, lack of psychomotor development, and autonomic abnormalities including labile cardiovascular function, lack of corneal reflexes leading to corneal scarring, areflexia, and absent axonal flare response after intradermal histamine injection (summary by Edvardson et al., 2012). For a discussion of genetic heterogeneity of hereditary sensory and autonomic neuropathy, see HSAN1 (162400).
Immunodeficiency, common variable, 7
MedGen UID:
762276
Concept ID:
C3542922
Disease or Syndrome
Menstrual cycle-dependent periodic fever
MedGen UID:
766332
Concept ID:
C3553418
Disease or Syndrome
Women show menstrual cycle-dependent physiologic changes in relation to sex hormone levels. Because ovulation triggers a significant change in the hormonal milieu that is similar to local inflammation, a 0.5 to 1.0 degree Celsius increase in basal body temperature after ovulation is commonly associated with progesterone secretion and is believed to be triggered by the induction of several inflammatory cytokines. Rare menstrual cycle-dependent febrile episodes have been reported, some of which have shown a luteal-phase-dependent pattern (summary by Jiang et al., 2012).
Lymphoproliferative syndrome 2
MedGen UID:
767454
Concept ID:
C3554540
Disease or Syndrome
Lymphoproliferative syndrome-2, also known as CD27 deficiency, is an autosomal recessive immunodeficiency disorder associated with persistent symptomatic EBV viremia, hypogammaglobulinemia, and impairment in specific antibody function resulting from impaired T cell-dependent B-cell responses and T-cell dysfunction (summary by van Montfrans et al., 2012). The phenotype can vary significantly, from asymptomatic borderline-low hypogammaglobulinemia, to a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation (summary by Salzer et al., 2013). For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240).
Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency
MedGen UID:
814919
Concept ID:
C3808589
Disease or Syndrome
Autosomal dominant IRF8 deficiency, or IMD32A, causes an abnormal peripheral blood myeloid phenotype with a marked loss of CD11C (ITGAX; 151510)-positive/CD1C (188340)-positive dendritic cells, resulting in selective susceptibility to mycobacterial infections (Hambleton et al., 2011).
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.
Aicardi-Goutieres syndrome 7
MedGen UID:
854829
Concept ID:
C3888244
Disease or Syndrome
Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with pathogenic variants in the AGS-related genes is not yet known.
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).
Severe combined immunodeficiency due to LCK deficiency
MedGen UID:
862670
Concept ID:
C4014233
Disease or Syndrome
A rare, combined T- and B-cell immunodeficiency characterized by failure to thrive, severe diarrhea, opportunistic infections, and abnormal T-cell differentiation and function due to LCK deficiency, leading to an important risk factor for inflammation and autoimmunity.
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).
Familial cold autoinflammatory syndrome 4
MedGen UID:
863713
Concept ID:
C4015276
Disease or Syndrome
A rare hereditary periodic fever syndrome with characteristics of infantile or childhood onset of episodes of fever and cold-induced urticaria-like rash and arthralgia. Ocular features such as conjunctivitis and uveitis may also be present. Presentation is typically mild and symptoms resolve without treatment in most cases.
Immunodeficiency 32B
MedGen UID:
865178
Concept ID:
C4016741
Disease or Syndrome
Immunodeficiency-32B is an autosomal recessive primary immunodeficiency characterized by recurrent infections resulting from variable defects in immune cell development or function, including monocytes, dendritic cells, and natural killer (NK) cells. Patients have particular susceptibility to viral disease (summary by Mace et al., 2017).
PERCHING syndrome
MedGen UID:
934709
Concept ID:
C4310742
Disease or Syndrome
PERCHING syndrome is an autosomal recessive multisystem disorder characterized by global developmental delay, dysmorphic facial features, feeding and respiratory difficulties with poor overall growth, axial hypotonia, and joint contractures. The features are variable, even within families, and may also include retinitis pigmentosa, cardiac or genitourinary anomalies, and abnormal sweating. Each letter of the PERCHING acronym represents 2 important phenotypic elements: Postural and Palatal abnormalities; Exophthalmos and Enteral-tube dependency/feeding issues; Respiratory distress and Retinitis pigmentosa; Contractures and Camptodactyly; Hypertelorism and Hirsutism; Intrauterine growth retardation (IUGR)/growth failure and Intellectual disability/developmental delay; Nevus flammeus and Neurologic malformations; and facial Gestalt/grimacing and Genitourinary abnormalities (Jeffries et al., 2019). Death in infancy or early childhood often occurs, although survival to the third decade has been reported. Some of the features, such as contractures, dysmorphic craniofacial features, and severe feeding difficulties, are reminiscent of Bohring-Opitz syndrome (605039) (summary by Kanthi et al., 2019 and Buers et al., 2020).
Hearing loss, autosomal dominant 34, with or without inflammation
MedGen UID:
1626346
Concept ID:
C4521680
Disease or Syndrome
DFNA34 is an autosomal dominant form of postlingual, slowly progressive sensorineural hearing loss with variable severity and variable additional features. Some patients have pure hearing loss without significant additional features, whereas some patients have features of an autoinflammatory disorder with systemic manifestations, including periodic fevers, arthralgias, and episodic urticaria. The disorder results from abnormally increased activation of the inflammatory pathway, and treatment with an IL1 receptor antagonist (see 147679) may be effective if started early (summary by Nakanishi et al., 2017).
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\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).\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.
Combined oxidative phosphorylation deficiency 34
MedGen UID:
1631307
Concept ID:
C4693450
Disease or Syndrome
COXPD34 is an autosomal recessive disorder resulting from a defect in mitochondrial function. The phenotype is variable, but may include congenital sensorineural deafness, increased serum lactate, and hepatic and renal dysfunction. Neurologic function is relatively preserved (summary by Menezes et al., 2015). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
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).
Mitochondrial complex 1 deficiency, nuclear type 13
MedGen UID:
1648370
Concept ID:
C4748770
Disease or Syndrome
Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination
MedGen UID:
1684142
Concept ID:
C5193057
Disease or Syndrome
A rare, genetic, neurometabolic disease characterized by microcephaly, short stature, epilepsy, cerebral hypomyelination, severe global developmental delay, and progressive spasticity. Macrocytic anemia and hyperthermia have also been reported in association. Brain imaging reveals delayed myelination with minimal progression over time, mild cerebellar atrophy and/or thin corpus callosum.
Immunodeficiency 60
MedGen UID:
1681890
Concept ID:
C5193072
Disease or Syndrome
Immunodeficiency-60 and autoimmunity (IMD60) is an autosomal dominant primary immunologic disorder characterized by inflammatory bowel disease and recurrent sinopulmonary infections. The age at symptom onset is highly variable, ranging from infancy to mid-adulthood. Laboratory studies show dysregulation of both B and T cells, with variably decreased immunoglobulin production, decreased T-regulatory cells, and overall impaired lymphocyte maturation (summary by Afzali et al., 2017).
Hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities
MedGen UID:
1672905
Concept ID:
C5193124
Disease or Syndrome
Hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities (HIDEA) is an autosomal recessive neurodevelopmental syndrome characterized by global developmental delay, poor or absent speech, hypotonia, variable ocular movement and visual abnormalities, and respiratory difficulties, including hypoventilation, and sleep apnea. Patients may have significant breathing problems during respiratory infections that may lead to early death (summary by Rahikkala et al., 2019).
Granulomatous disease, chronic, autosomal recessive, 5
MedGen UID:
1710326
Concept ID:
C5394542
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.
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).
Proteasome-associated autoinflammatory syndrome 5
MedGen UID:
1779962
Concept ID:
C5543027
Disease or Syndrome
Immunodeficiency 80 with or without congenital cardiomyopathy
MedGen UID:
1786417
Concept ID:
C5543344
Disease or Syndrome
Immunodeficiency-80 with or without congenital cardiomyopathy (IMD80) is an autosomal recessive immunologic disorder with variable manifestations. One patient with infantile-onset of chronic cytomegalovirus (CMV) infection associated with severely decreased NK cells has been reported. Another family with 3 affected fetuses showing restrictive cardiomyopathy and hypoplasia of the spleen and thymus has also been reported (summary by Baxley et al., 2021).
Developmental delay, impaired speech, and behavioral abnormalities
MedGen UID:
1794167
Concept ID:
C5561957
Disease or Syndrome
Developmental delay, impaired speech, and behavioral abnormalities (DDISBA) is characterized by global developmental delay apparent from early childhood. Intellectual disability can range from mild to severe. Additional variable features may include dysmorphic facial features, seizures, hypotonia, motor abnormalities such as Tourette syndrome or dystonia, and hearing loss (summary by Cousin et al., 2021).
DEGCAGS syndrome
MedGen UID:
1794177
Concept ID:
C5561967
Disease or Syndrome
DEGCAGS syndrome is an autosomal recessive syndromic neurodevelopmental disorder characterized by global developmental delay, coarse and dysmorphic facial features, and poor growth and feeding apparent from infancy. Affected individuals have variable systemic manifestations often with significant structural defects of the cardiovascular, genitourinary, gastrointestinal, and/or skeletal systems. Additional features may include sensorineural hearing loss, hypotonia, anemia or pancytopenia, and immunodeficiency with recurrent infections. Death in childhood may occur (summary by Bertoli-Avella et al., 2021).
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).
Systemic lupus erythematosus 17
MedGen UID:
1804329
Concept ID:
C5676884
Disease or Syndrome
Systemic lupus erythematosus-17 (SLE17) is an X-linked dominant autoimmune disorder characterized by onset of systemic autoinflammatory symptoms in the first decades of life. Only affected females have been reported. Features may include classic features of SLE, such as malar rash and arthralgias, or can include less common entities such as hemiplegia and neuromyelitis optica (NMO). Laboratory studies show the presence of autoantibodies and enhanced NFKB (164011) signaling, the latter being consistent with a gain-of-function effect (Brown et al., 2022). For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700.
Stüve-Wiedemann syndrome 1
MedGen UID:
1803541
Concept ID:
C5676888
Disease or Syndrome
Stuve-Wiedemann syndrome is an autosomal recessive disorder characterized by bowing of the long bones and other skeletal anomalies, episodic hyperthermia, respiratory distress, and feeding difficulties usually resulting in early death (Dagoneau et al., 2004). See also 'classic' Schwartz-Jampel syndrome type 1 (SJS1; 255800), a phenotypically similar but genetically distinct disorder caused by mutation in the HSPG2 gene (142461) on chromosome 1p36. Genetic Heterogeneity of Stuve-Wiedemann Syndrome Stuve-Wiedemann syndrome-2 (STWS2; 619751) is caused by mutation in the IL6ST gene (600694) on chromosome 5q11.
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).
Cholestasis, progressive familial intrahepatic, 9
MedGen UID:
1809292
Concept ID:
C5676973
Disease or Syndrome
Progressive familial intrahepatic cholestasis-9 (PFIC9) is an autosomal recessive disorder characterized by onset of cholestasis associated with increased serum gamma-glutamyltransferase (GGT) in infancy or early childhood. Affected individuals have hepatosplenomegaly and may have portal hypertension or upper gastrointestinal bleeding. Liver biopsy shows fibrosis, cirrhosis, bile duct proliferation, and abnormal bile duct morphology. The disorder is thought to result from ciliary defects in cholangiocytes, consistent with a ciliopathy that appears to be restricted to the liver. Treatment with ursodeoxycholic acid (UDCA) or liver transplant is effective (Luan et al., 2021). For a discussion of genetic heterogeneity of progressive familial intrahepatic cholestasis, see PFIC1 (211600).
Autoinflammatory-pancytopenia syndrome due to DNASE2 deficiency
MedGen UID:
1803642
Concept ID:
C5676977
Disease or Syndrome
Autoinflammatory-pancytopenia syndrome (AIPCS) is an autosomal recessive disorder characterized by severe anemia and thrombocytopenia apparent from early infancy, hepatosplenomegaly, and recurrent fevers associated with a hyperinflammatory state. Additional systemic features may include chronic diarrhea, proteinuria with renal disease, liver fibrosis with elevated liver enzymes, deforming arthropathy, and vasculitic skin lesions. Some patients may have motor delay or learning difficulties associated with subcortical white matter lesions on brain imaging. Laboratory studies show increased levels of proinflammatory cytokines and increased expression of interferon-stimulated genes (ISGs), consistent with a type I interferonopathy (Rodero et al., 2017). Treatment with a JAK (see 147795) inhibitor (baricitinib) may be effective (Hong et al., 2020).
Immunodeficiency 105
MedGen UID:
1809425
Concept ID:
C5677005
Disease or Syndrome
Immunodeficiency-105 (IMD105) is an autosomal recessive disorder characterized by onset of recurrent infections in early infancy. Manifestations may include pneumonia, dermatitis, and lymphadenopathy. B-cell lymphoma was reported in 1 patient. Laboratory studies show decreased or absent numbers of nonfunctional T cells, normal or increased levels of B cells, hypogammaglobulinemia, and normal or low NK cells. The disorder is caused by a deficiency of transmembrane protein CD45 (PTPRC) on leukocytes, which plays an important role in T- and B-cell development (Cale et al., 1997; Kung et al., 2000). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive SCID, see 601457.
Mitochondrial complex 3 deficiency, nuclear type 11
MedGen UID:
1824032
Concept ID:
C5774259
Disease or Syndrome
Mitochondrial complex III deficiency nuclear type 11 (MC3DN11) is an autosomal recessive disorder characterized by recurrent episodes of severe lactic acidosis, hyperammonemia, hypoglycemia, and encephalopathy (Vidali et al., 2021) For a discussion of genetic heterogeneity of mitochondrial complex III deficiency, see MC3DN1 (124000).
Leukoencephalopathy with vanishing white matter 1
MedGen UID:
1830482
Concept ID:
C5779972
Disease or Syndrome
Any leukoencephalopathy with vanishing white matter in which the cause of the disease is a variation in the EIF2B1 gene.
Congenital disorder of deglycosylation 1
MedGen UID:
989503
Concept ID:
CN306977
Disease or Syndrome
Individuals with NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) typically display a clinical tetrad of developmental delay / intellectual disability in the mild to profound range, hypo- or alacrima, elevated liver transaminases that may spontaneously resolve in childhood, and a complex hyperkinetic movement disorder that can include choreiform, athetoid, dystonic, myoclonic, action tremor, and dysmetric movements. About half of affected individuals will develop clinical seizures. Other findings may include obstructive and/or central sleep apnea, oral motor defects that affect feeding ability, auditory neuropathy, constipation, scoliosis, and peripheral neuropathy.

Professional guidelines

PubMed

Sykes EA, Wu V, Beyea MM, Simpson MTW, Beyea JA
Can Fam Physician 2020 Apr;66(4):251-257. PMID: 32273409Free PMC Article
Gaitonde DY, Moore FC, Morgan MK
Am Fam Physician 2019 Dec 15;100(12):751-758. PMID: 31845781
Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Tleyjeh IM, Rybak MJ, Barsic B, Lockhart PB, Gewitz MH, Levison ME, Bolger AF, Steckelberg JM, Baltimore RS, Fink AM, O'Gara P, Taubert KA; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council
Circulation 2015 Oct 13;132(15):1435-86. Epub 2015 Sep 15 doi: 10.1161/CIR.0000000000000296. PMID: 26373316

Curated

UK NICE Guideline NG143, Fever in under 5s: assessment and initial management, 2021

Recent clinical studies

Etiology

Tuells J, Henao-Martínez AF, Franco-Paredes C
Arch Med Res 2022 Nov;53(7):649-657. Epub 2022 Oct 28 doi: 10.1016/j.arcmed.2022.10.005. PMID: 36404585
Ludwig J, McWhinnie H
Br J Nurs 2019 May 23;28(10):610-618. doi: 10.12968/bjon.2019.28.10.610. PMID: 31116598
Eldin C, Mélenotte C, Mediannikov O, Ghigo E, Million M, Edouard S, Mege JL, Maurin M, Raoult D
Clin Microbiol Rev 2017 Jan;30(1):115-190. doi: 10.1128/CMR.00045-16. PMID: 27856520Free PMC Article
Dayal R, Agarwal D
Indian J Pediatr 2016 Jan;83(1):38-43. Epub 2015 Mar 1 doi: 10.1007/s12098-015-1724-4. PMID: 25724501
Wing R, Dor MR, McQuilkin PA
Emerg Med Clin North Am 2013 Nov;31(4):1073-96. Epub 2013 Sep 26 doi: 10.1016/j.emc.2013.07.006. PMID: 24176480

Diagnosis

Bakalli I, Klironomi D, Kola E, Celaj E
Minerva Pediatr (Torino) 2022 Oct;74(5):568-578. Epub 2022 Jul 13 doi: 10.23736/S2724-5276.22.06680-0. PMID: 35822579
Wright WF, Mulders-Manders CM, Auwaerter PG, Bleeker-Rovers CP
Am J Med 2022 Feb;135(2):173-178. Epub 2021 Aug 24 doi: 10.1016/j.amjmed.2021.07.038. PMID: 34437835
Grebenyuk V, Kryštůfková O, Gregová M, Sokalská-Jurkiewicz M, Steinbauerová R, Sukovská M, Gahérová L, Zubatá I, Gregorová J, Kaliská L, Roháčová H, Trojánek M
Vnitr Lek 2021 Winter;67(1):32-42. PMID: 33752399
Mulders-Manders C, Simon A, Bleeker-Rovers C
Clin Med (Lond) 2015 Jun;15(3):280-4. doi: 10.7861/clinmedicine.15-3-280. PMID: 26031980Free PMC Article
McCarthy PL
Pediatr Rev 1998 Dec;19(12):401-7; quiz 408. doi: 10.1542/pir.19-12-401. PMID: 9849069

Therapy

Goetzl L
Am J Obstet Gynecol 2023 May;228(5S):S1274-S1282. Epub 2023 Mar 20 doi: 10.1016/j.ajog.2022.11.002. PMID: 36997396
Marzi A, Mire CE
BioDrugs 2019 Feb;33(1):9-14. doi: 10.1007/s40259-018-0329-7. PMID: 30604389
Griffiths PD
Rev Med Virol 2014 Nov;24(6):363-4. Epub 2014 Oct 15 doi: 10.1002/rmv.1812. PMID: 25318448
Norrby R
Clin Microbiol Infect 2014 May;20 Suppl 5:92-4. Epub 2014 Jan 20 doi: 10.1111/1469-0691.12442. PMID: 24438016
Thaver D, Zaidi AK, Critchley JA, Azmatullah A, Madni SA, Bhutta ZA
Cochrane Database Syst Rev 2008 Oct 8;(4):CD004530. doi: 10.1002/14651858.CD004530.pub3. PMID: 18843659

Prognosis

Grønberg BH, Killingberg KT, Fløtten Ø, Brustugun OT, Hornslien K, Madebo T, Langer SW, Schytte T, Nyman J, Risum S, Tsakonas G, Engleson J, Halvorsen TO
Lancet Oncol 2021 Mar;22(3):321-331. doi: 10.1016/S1470-2045(20)30742-7. PMID: 33662285
Tsur AM, Watad A, Gendelman O, Nissan D, Cohen AD, Amital H
Rheumatology (Oxford) 2021 Dec 1;60(12):5642-5646. doi: 10.1093/rheumatology/keab159. PMID: 33590869
Eltorai AEM, Baird GL, Eltorai AS, Healey TT, Agarwal S, Ventetuolo CE, Martin TJ, Chen J, Kazemi L, Keable CA, Diaz E, Pangborn J, Fox J, Connors K, Sellke FW, Elias JA, Daniels AH
JAMA Surg 2019 Jul 1;154(7):579-588. doi: 10.1001/jamasurg.2019.0520. PMID: 30969332Free PMC Article
Nazir S, Elgin E, Loynd R, Zaman M, Donato A
Am J Cardiol 2019 Apr 15;123(8):1239-1243. Epub 2019 Mar 17 doi: 10.1016/j.amjcard.2019.01.033. PMID: 30890259
Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Martinez-Silveira MS, Stein C, Abela-Ridder B, Ko AI
PLoS Negl Trop Dis 2015;9(9):e0003898. Epub 2015 Sep 17 doi: 10.1371/journal.pntd.0003898. PMID: 26379143Free PMC Article

Clinical prediction guides

Stösser S, Gotthardt M, Lindner-Pfleghar B, Jüttler E, Kassubek R, Neugebauer H
Stroke 2021 Jul;52(7):2284-2291. Epub 2021 Apr 29 doi: 10.1161/STROKEAHA.120.033396. PMID: 33910366
Vacirca A, Faggioli G, Pini R, Freyrie A, Indelicato G, Fenelli C, Bacchi Reggiani ML, Vasuri F, Pasquinelli G, Stella A, Gargiulo M
J Vasc Surg 2020 May;71(5):1771-1780. Epub 2019 Dec 17 doi: 10.1016/j.jvs.2019.09.030. PMID: 31862201
Yuan SM, Lin H
Ann Thorac Cardiovasc Surg 2018 Dec 20;24(6):279-287. Epub 2018 Aug 29 doi: 10.5761/atcs.ra.18-00136. PMID: 30158332Free PMC Article
Rampersad A, Mukundan D
Curr Opin Pediatr 2009 Feb;21(1):139-44. doi: 10.1097/MOP.0b013e32832130d2. PMID: 19242251
Rolston KV
Int J Antimicrob Agents 2000 Oct;16(2):113-5. doi: 10.1016/s0924-8579(00)00215-6. PMID: 11053790

Recent systematic reviews

Sandroni C, Natalini D, Nolan JP
Crit Care 2022 Nov 24;26(1):361. doi: 10.1186/s13054-022-04238-z. PMID: 36434649Free PMC Article
Kuehn R, Stoesser N, Eyre D, Darton TC, Basnyat B, Parry CM
Cochrane Database Syst Rev 2022 Nov 24;11(11):CD010452. doi: 10.1002/14651858.CD010452.pub2. PMID: 36420914Free PMC Article
Tan E, Braithwaite I, McKinlay CJD, Dalziel SR
JAMA Netw Open 2020 Oct 1;3(10):e2022398. doi: 10.1001/jamanetworkopen.2020.22398. PMID: 33125495Free PMC Article
Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, Langston AA, Nastoupil LJ, Rajotte M, Rolston K, Strasfeld L, Flowers CR
J Clin Oncol 2018 May 10;36(14):1443-1453. Epub 2018 Feb 20 doi: 10.1200/JCO.2017.77.6211. PMID: 29461916
Mewasingh LD
BMJ Clin Evid 2014 Jan 31;2014 PMID: 24484859Free PMC Article

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    Curated

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      UK NICE Guideline NG143, Fever in under 5s: assessment and initial management, 2021

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