{"Name":"Activated PI3K-delta syndrome","DiseaseID__c":"GARD:0011983","id":11983,"encodedName":"activated-pi3k-delta-syndrome","IsDeleted":false,"Disease_Name_Full__c":"Activated PI3K-delta syndrome","Xref_IDs__c":"711480000; C585640; CN295305; MEDGEN:978173; MONDO:0018338; NBK611655; ORPHA:397596","USA_Estimate__c":"1,000","No_of_Specialist_Tagsa__c":3,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":1,"No_of_HHS_records__c":0,"World_Estimate__c":"1 to 8,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":2,"No_of_Disease_Descriptions__c":2,"Disease_Characteristics_Score__c":8,"No_of_Age_at_Onset__c":3,"Description_Source__c":"ORPHA:397596","Disease_Description__c":"A rare, genetic, primary immunodeficiency disease characterized by increased susceptibility to recurrent and/or severe bacterial and viral infections (in particular, sinopulmonary bacterial and herpesvirus infections), chronic benign lymphoproliferation (manifesting as lymphadenopathy, hepatosplenomegaly and focal nodular lymphoid hyperplasia), and/or autoimmune disease (including immune cytopenias, juvenile arthritis, glomerulonephritis and sclerosing cholangitis). Immunophenotypically, variable degrees of agammaglobulinemia with increased IgM levels, increased circulating transitional B cells, decreased naïve CD4 and CD8 T-cells with increased CD8 effector/memory T cells are observed.","GARD_Name__c":"Activated PI3K-delta syndrome","GARD_Synonym__c":"apds; senescent t-cells-lymphadenopathy-immunodeficiency syndrome due to p110delta-activating mutation","Curated_Disease_Description_Source__c":"ORPHA:397596","Curated_Disease_Description__c":"Activated PI3K-delta syndrome (also known as APDS) is a disorder that impairs the immune system. Individuals with this condition often have low numbers of white blood cells (lymphopenia), particularly B cells and T cells. Normally, these cells recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. The severity of activated PI3K-delta syndrome varies widely. Some people may have multiple, severe infections while others show mild  symptoms to none at all. Most commonly, people with activated PI3K-delta syndrome develop recurrent infections that begin in childhood, particularly in the lungs, sinuses, and ears. Over time, recurrent respiratory tract infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. People with activated PI3K-delta syndrome may also have chronic active viral infections, such as Epstein-Barr virus, herpes simplex virus, or cytomegalovirus infections. Another possible feature of activated PI3K-delta syndrome is abnormal clumping of white blood cells. These clumps can lead to enlarged lymph nodes (lymphadenopathy) or an enlarged spleen (splenomegaly). The white blood cells can also build up to form solid masses (nodular lymphoid hyperplasia), usually in the moist lining of the airways or intestines. While nodular lymphoid hyperplasia is not cancerous (benign), activated PI3K-delta syndrome  increases the risk of developing forms of blood cancer called Hodgkin lymphoma and non-Hodgkin lymphoma. Some people with activated PI3K-delta syndrome develop autoimmunity, which occurs when the body attacks its own tissues and organs by mistake. There are two types of activated PI3K-delta syndrome, each with different genetic causes.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"at a variety of ages","SourceID__c":"ORPHA:397596","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Grouping","MONDO_ID__c":"MONDO:0018338","ORPHANET_ID__c":"ORPHA:397596","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Síndrome de pi3k-delta activado","Spanish_Description_Source__c":null,"Spanish_Description__c":null,"Spanish_Disease_Name__c":"síndrome de pi3k-delta activado","Spanish_GARD_Synonym__c":"apds; pasli; síndrome de células-t senescentes-linfadenopatía-inmunodeficiencia por una mutación activadora de p110delta; síndrome de células-t senescentes-linfadenopatía-inmunodeficiencia por una mutación activadora de pi3k delta; síndrome de p110-delta activado","Category_Linearization__c":"ORPHA:98004","icd10_id__c":null,"mesh_id__c":null,"omim_id__c":null,"snomed_id__c":null,"umls_id__c":null,"GARD_Disease__c":[{"Curated_Disease_Description__c":"Activated PI3K-delta syndrome (also known as APDS) is a disorder that impairs the immune system. Individuals with this condition often have low numbers of white blood cells (lymphopenia), particularly B cells and T cells. Normally, these cells recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. The severity of activated PI3K-delta syndrome varies widely. Some people may have multiple, severe infections while others show mild  symptoms to none at all. Most commonly, people with activated PI3K-delta syndrome develop recurrent infections that begin in childhood, particularly in the lungs, sinuses, and ears. Over time, recurrent respiratory tract infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. People with activated PI3K-delta syndrome may also have chronic active viral infections, such as Epstein-Barr virus, herpes simplex virus, or cytomegalovirus infections. Another possible feature of activated PI3K-delta syndrome is abnormal clumping of white blood cells. These clumps can lead to enlarged lymph nodes (lymphadenopathy) or an enlarged spleen (splenomegaly). The white blood cells can also build up to form solid masses (nodular lymphoid hyperplasia), usually in the moist lining of the airways or intestines. While nodular lymphoid hyperplasia is not cancerous (benign), activated PI3K-delta syndrome  increases the risk of developing forms of blood cancer called Hodgkin lymphoma and non-Hodgkin lymphoma. Some people with activated PI3K-delta syndrome develop autoimmunity, which occurs when the body attacks its own tissues and organs by mistake. There are two types of activated PI3K-delta syndrome, each with different genetic causes.","Curated_Disease_Description_Source__c":"ORPHA:397596","GARD_Synonym__c":"apds; senescent t-cells-lymphadenopathy-immunodeficiency syndrome due to p110delta-activating mutation","Name":"Activated PI3K-delta syndrome","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Immunodeficiency UK","Website__c":"https://www.immunodeficiencyuk.org/"},{"Account_Name__c":"United States Immunodeficiency Network","Website__c":"https://www.usidnet.org"},{"Account_Name__c":"Jeffrey Modell Foundation","Website__c":"https://www.info4pi.org/"},{"Account_Name__c":"Immune Deficiency Foundation","Website__c":"https://www.primaryimmune.org/"},{"Account_Name__c":"Canadian Immunodeficiencies Patient Organization","Website__c":"http://www.cipo.ca/"},{"Account_Name__c":"Immune Deficiencies Foundation Australia","Website__c":"http://www.idfa.org.au/"}],"GARD_Disease_Tag__c":[{"Tag_Name__c":"Genetics","Tag_Category__c":"Cause;Disease Category;Specialist","category_description":"Genetic diseases affect the DNA, or genetic instructions, which directs how tissues, organs, and body systems function.","curated_tag_name":"Genetic diseases"},{"Tag_Name__c":"Immunology","Tag_Category__c":"Specialist"},{"Tag_Name__c":"Primary Immune Deficiencies","Tag_Category__c":"Account","curated_tag_name":"Primary immunodeficiency"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Childhood","Provided_By__c":"ORPHA:397596"},{"Age_At_Onset__c":"Adult","Provided_By__c":"ORPHA:397596"},{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:397596"}],"Diagnosis__c":[{"Type__c":"GTR","Curie__c":"MEDGEN:C3714976"}],"External_Identifier_Disease__c":[{"URL__c":"https://raresource.nih.gov/diseases/filter/0011983","Source__c":"RareSource"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=711480000","Source__c":"MONDO:0018338","Xref__c":"711480000"},{"URL__c":"https://www.orpha.net/en/disease/detail/397596","Source__c":"CN295305; MONDO:0018338","Xref__c":"ORPHA:397596"},{"URL__c":"https://www.ncbi.nlm.nih.gov/mesh/C585640","Source__c":"MONDO:0018338","Xref__c":"C585640"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0018338","Source__c":"GARD:0011983","Xref__c":"MONDO:0018338"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=978173","Source__c":"CN295305","Xref__c":"MEDGEN:978173"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/CN295305","Source__c":"CN295305","Xref__c":"CN295305"},{"URL__c":"https://www.ncbi.nlm.nih.gov/books/NBK611655","Source__c":"Gene Review","Xref__c":"NBK611655"}],"Inheritance__c":["Autosomal dominant"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An abnormally increased level of immunoglobulin M in blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003496","HPO_Synonym__c":"Increased IgM levels; Increased levels of IgM","HPO_Name__c":"Increased circulating IgM level","Feature_System__c":"Immune System; Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000403","HPO_Synonym__c":"Frequent otitis media; Multiple episodes of otitis media; Otitis media, recurrent; Recurrent episodes of otitis media; Recurrent middle ear infection; Susceptibility to otitis media","HPO_Name__c":"Recurrent otitis media","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A decreased magnitude of the sensory perception of sound.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000365","HPO_Synonym__c":"Deafness; Hearing defect; Hearing impairment; Hypacusis","HPO_Name__c":"Hearing impairment","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Increased susceptibility to upper and lower respiratory tract infections, as manifested by recurrent episodes of upper and lower respiratory tract infections.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0200117","HPO_Name__c":"Recurrent upper and lower respiratory tract infections","Feature_System__c":"Respiratory system; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"The occurrence of an immune reaction against the organism's own cells or tissues.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002960","HPO_Synonym__c":"Autoimmune condition; Autoimmune disease; Autoimmune disorder; Autoimmunity","HPO_Name__c":"Autoimmunity","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A chronic form of sinusitis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011109","HPO_Name__c":"Chronic sinusitis","Feature_System__c":"Musculoskeletal System; Respiratory system; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A cancer originating in lymphocytes and presenting as a solid tumor of lymhpoid cells.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002665","HPO_Synonym__c":"Cancer of lymphatic system","HPO_Name__c":"Lymphoma","Feature_System__c":"Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Inflammation of the tonsils that has occurred repeatedly. The definition of recurrent may vary somewhat, but the criteria used recently as a measure of severity were five or more episodes of true tonsillitis per year, symptoms recurring for at least a year, and episodes that are disabling and that prevent normal functioning. In some cases recurrent tonsillitis may be related to immunosusceptibility. Evidence exists for a genetic predisposition for recurrent tonsillitis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011110","HPO_Synonym__c":"Recurrent inflammation of tonsils","HPO_Name__c":"Recurrent tonsillitis","Feature_System__c":"Cardiovascular System; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Abnormal increased size of the spleen.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001744","HPO_Synonym__c":"Increased spleen size; Large spleen","HPO_Name__c":"Splenomegaly","Feature_System__c":"Cardiovascular System; Immune System; Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abnormality of the intestine. The closely related term enteropathy is used to refer to any disease of the intestine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002242","HPO_Synonym__c":"Abnormality of the intestine; Enteropathy","HPO_Name__c":"Abnormal intestine morphology","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An unusually severe form of varicella zoster virus (VZV) infection. In the majority of the cases, especially in children, varicella is a very mild infection characterized by skin lesions, low grade fever and malaise. Severe infection is characterized by manifestations including VZV pneumonia, hepatitis, meningitis, and disseminated varicella.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0032170","HPO_Name__c":"Severe varicella zoster infection","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An abnormally decreased level of immunoglobulin in blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0004313","HPO_Synonym__c":"Decreased antibody level in blood; Decreased circulating antibody level; Decreased immunoglobulin level; Decreased serum immunoglobulin; Hypogammaglobulinemia; Immunoglobulin deficiency; Reduced immunoglobulin levels","HPO_Name__c":"Decreased circulating immunoglobulin concentration","Feature_System__c":"Immune System; Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002110","HPO_Synonym__c":"Permanent enlargement of the airways of the lungs","HPO_Name__c":"Bronchiectasis","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Abnormally increased size of the liver.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002240","HPO_Synonym__c":"Enlarged liver","HPO_Name__c":"Hepatomegaly","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Enlargement (swelling) of a lymph node.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002716","HPO_Synonym__c":"Lymph node hyperplasia; Swollen lymph nodes","HPO_Name__c":"Lymphadenopathy","Feature_System__c":"Cardiovascular System; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Inflammation of any part of the lung parenchyma.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002090","HPO_Synonym__c":"Pneumonia","HPO_Name__c":"Pneumonia","Feature_System__c":"Respiratory system; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Inflammation of a joint.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001369","HPO_Synonym__c":"Arthritis; Joint inflammation","HPO_Name__c":"Arthritis","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012758","HPO_Synonym__c":"NDD","HPO_Name__c":"Neurodevelopmental delay","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An unusually severe infection by cytomegalovirus.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0031692","HPO_Name__c":"Severe cytomegalovirus infection","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001508","HPO_Synonym__c":"Faltering weight; FTT; Postnatal failure to thrive; Weight faltering","HPO_Name__c":"Failure to thrive","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An unusually severe Epstein Barr virus (EBV) infection.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0031693","HPO_Synonym__c":"Fulminant infectious mononucleosis; Severe EBV infection","HPO_Name__c":"Severe Epstein Barr virus infection","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A lymphoproliferative abnormality of the intestine characterized by numerous visible mucosal nodules measuring up to, and rarely exceeding, 0.5 cm in diameter Histologically, hyperplastic lymphoid follicles with large germinal centers are seen in the lamina propria and superficial submucosa. There is enlargement of the mucosal B cell follicles caused by hyperplasia of the follicle centers; surrounded by a normal appearing mantle zone. Disease may involve the stomach, the entire small intestine, and the large intestine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011956","HPO_Name__c":"Intestinal lymphoid nodular hyperplasia","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Head circumference below 2 standard deviations below the mean for age and sex.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000252","HPO_Synonym__c":"Abnormally small cranium; Abnormally small skull; Decreased circumference of cranium; Decreased size of cranium; Decreased size of skull; Reduced head circumference; small cranium; Small head circumference","HPO_Name__c":"Microcephaly","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:397596","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"The absolute number of B cells in the blood, per microlitre is below the lower limit of normal of the reference range for the appropriate sex and age-group.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0010976","HPO_Synonym__c":"B cell deficiency; B cell lymphopenia; B lymphocytopenia; Decreased B cell count; Low B cell count; Reduction in B cell number","HPO_Name__c":"Decreased total B cell count","Feature_System__c":"Immune System; Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics"],"Disease Category":["Genetics"],"Specialist":["Genetics","Immunology","Pediatrics"],"Account":["Primary Immune Deficiencies"]},"synonyms":["apds"," senescent t-cells-lymphadenopathy-immunodeficiency syndrome due to p110delta-activating mutation"]}