MedGen

The WAS-related disorders, which include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked congenital neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes caused by pathogenic variants in WAS. WAS-related disorders usually present in infancy. Affected males have thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; eczema; and recurrent bacterial and viral infections, particularly of the ear. At least 40% of those who survive the early complications develop one or more autoimmune conditions including hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, rheumatoid arthritis, vasculitis, and immune-mediated damage to the kidneys and liver. Individuals with a WAS-related disorder, particularly those who have been exposed to Epstein-Barr virus (EBV), are at increased risk of developing lymphomas, which often occur in unusual, extranodal locations including the brain, lung, or gastrointestinal tract. Males with XLT have thrombocytopenia with small platelets; other complications of Wiskott-Aldrich syndrome, including eczema and immune dysfunction, are usually mild or absent. Males with XLN have congenital neutropenia, myeloid dysplasia, and lymphoid cell abnormalities. [from GeneReviews]

Caspase 8 deficiency is a syndrome of lymphadenopathy and splenomegaly, marginal elevation of 'double-negative T cells' (DNT; T-cell receptor alpha/beta+, CD4-/CD8-), defective FAS-induced apoptosis, and defective T-, B-, and natural killer (NK)-cell activation, with recurrent bacterial and viral infections (summary by Madkaikar et al., 2011). [from OMIM]

Mannose-binding lectin (MBL) deficiency, defined as MBL protein level of less than 100 ng/ml, is present in about 5% of people of European descent and in about 10% of sub-Saharan Africans. Most MBL-deficient adults appear healthy, but low levels of MBL are associated with increased risk of infection in toddlers, in cancer patients undergoing chemotherapy, and in organ-transplant patients receiving immunosuppressive drugs, particularly recipients of liver transplants (review by Degn et al., 2011). MBL is a soluble molecule that can activate the lectin pathway of the complement system; deficiency may thus lead to defects in the complement system (summary by Garcia-Laorden et al., 2008). Genetic Heterogeneity of Lectin Complement Activation Pathway Defects See also LCAPD2 (613791), caused by variation in the MASP2 gene (605102) on chromosome 1p36, and LCAPD3 (613860), caused by variation in the FCN3 gene (604973) on chromosome 1p36. [from OMIM]

Any severe combined immunodeficiency in which the cause of the disease is a mutation in the CD247 gene. [from MONDO]

Herpes simplex virus (HSV)-1 is most often associated with infection of the oral mucosa. Primary infection is most commonly asymptomatic, but it may lead to symptoms usually involving the mucosa and skin. Following replication at the infection site, HSV-1 enters the epithelial endings of sensory neurons and travels up the trigeminal cranial nerves to the trigeminal ganglia, where latent infection is established. Reactivation of HSV-1, usually in the form of herpes labialis (cold sores), may occur in 20 to 40% of the population. HSV-1 seroprevalence is high, with over 85% of adults between the ages of 20 and 40 years infected. HSV-1 rarely infects the central nervous system (CNS), resulting in herpes simplex encephalitis (HSE), with an incidence of 2 to 4 per 1,000,000 people per year. In HSE, HSV-1 invades and replicates in neurons and glial cells, where focal necrotizing infections occur, primarily affecting the temporal and subfrontal regions of the brain. Untreated, HSE is fatal in at least 70% of cases, although the mortality and morbidity have been drastically reduced with antiviral therapy. Approximately one-third of all HSE cases are due to primary infections, and 30% of all HSE cases occur in children under the age of 20 years. Among children, HSE peaks between 3 months and 3 years of age, coinciding with the time of primary infection. In a subset of children, HSE results from a series of monogenic primary immunodeficiencies that impair UNC93B1- and TLR3 (603029)-dependent production of IFNA (147660)/IFNB (147640) and IFNG (147570) in the CNS (summary by Sancho-Shimizu et al., 2007). Genetic Heterogeneity of Susceptibility to Acute Infection-Induced Encephalopathy, including Herpes Simplex Encephalitis (HSE) For other forms of susceptibility to acute infection-induced encephalopathy, see herpes-specific IIAE2 (613002), caused by mutation in the TLR3 gene (603029) on chromosome 4q35; IIAE3 (608033), caused by mutation in the RANBP2 gene (601181) on chromosome 2q12; IIAE4 (614212), caused by mutation in the CPT2 gene (600650) on chromosome 1p32; herpes-specific IIAE5 (614849), caused by mutation in the TRAF3 gene (601896) on chromosome 14q32; herpes-specific IIAE6 (614850), caused by mutation in the TICAM1 gene (607601) on chromosome 19p13; herpes-specific IIAE7 (616532), caused by mutation in the IRF3 gene (603734) on chromosome 19q13; herpes-specific IIAE8 (617900), caused by mutation in the TBK1 gene (604834) on chromosome 12q14; IIAE9 (618426), caused by mutation in the NUP214 gene (114350) on chromosome 9q34; herpes-specific IIAE10 (619396), caused by mutation in the SNORA31 (619378) on chromosome 13q14; IIAE11 (619441), caused by mutation in the DBR1 gene (607024) on chromosome 3q22; and IIAE12 (620461), caused by mutation in the RNH1 gene (173320) on chromosome 11p15. [from OMIM]

Immunodeficiency-62 (IMD62) is an autosomal recessive primary immunologic disorder clinically characterized by onset of recurrent upper and lower respiratory infections late in the first decade of life. Patients may also have increased viral susceptibility to varicella zoster virus (VZV) or herpes simplex virus (HSV). Laboratory studies show impaired antibody response to vaccination, low levels of circulating memory B cells, and almost undetectable antibodies. There is also evidence of secondary T-cell dysfunction. The disorder may result from disturbed actin cytoskeleton dynamics causing impaired lymphocyte migration (summary by Bouafia et al., 2019). [from OMIM]

Hatipoglu immunodeficiency syndrome (HATIS) is an autosomal recessive immunologic disorder characterized by childhood onset of failure to thrive, skin manifestations, pancytopenia, and susceptibility to recurrent infections (Harapas et al., 2022). [from OMIM]

Increased susceptibility to herpesvirus, as manifested by recurrent episodes of herpesvirus. [from HPO]