{"Name":"Familial cold autoinflammatory syndrome 3","DiseaseID__c":"GARD:0017369","id":17369,"encodedName":"familial-cold-autoinflammatory-syndrome-3","IsDeleted":false,"Disease_Name_Full__c":"Familial cold autoinflammatory syndrome 3","Xref_IDs__c":"C3280914; DOID:0090064; MEDGEN:482544; MONDO:0013766; OMIM:614468; ORPHA:300359","USA_Estimate__c":"1,000","No_of_Specialist_Tagsa__c":5,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":0,"World_Estimate__c":"1 to 8,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":0,"No_of_Disease_Descriptions__c":4,"Disease_Characteristics_Score__c":8,"No_of_Age_at_Onset__c":2,"Description_Source__c":"MONDO:0013766","Disease_Description__c":"A rare, hereditary, immune deficiency with skin involvement characterized by early-onset cold urticaria after generalized exposure to cold air or evaporative cooling and not after contact with cold objects. Additional immunologic abnormalities are often present - antibody deficiency, recurrent infections, autoimmune disease and symptomatic allergic disease.","GARD_Name__c":"Familial cold autoinflammatory syndrome 3","GARD_Synonym__c":"antibody deficiency and immune dysregulation, plcg2-associated; facu; familial atypical cold urticaria; familial cold autoinflammatory syndrome caused by mutation in plcg2; familial cold autoinflammatory syndrome type 3; familial cold urticaria with common variable immunodeficiency; fcas3; plaid; plcg2 familial cold autoinflammatory syndrome; plcg2-associated antibody deficiency and immune dysregulation","Curated_Disease_Description_Source__c":"ORPHA:300359","Curated_Disease_Description__c":"PLCG2-associated antibody deficiency and immune dysregulation (PLAID) is an immune system disorder characterized by an allergic reaction to cold temperatures. Other immune system problems can also occur. The hallmark feature of PLAID is the development of a red, itchy rash (hives) when the skin is exposed to cool temperatures, which is known as cold urticaria. In PLAID, the hives typically develop in response to evaporative cooling, such as when a cool breeze or air conditioning blows on damp or sweaty skin. Being in a cold swimming pool can also trigger hives. In contrast, people with PLAID do not have a reaction when they touch a cold object, like an ice cube. (The ice cube test is a common test for a cold allergy; it triggers a reaction in people with other forms of cold urticaria, which usually begin later in life than PLAID.) However, some people with PLAID do experience a burning sensation in their throats when they eat cold foods, like ice cream. In PLAID, the hives go away once the skin warms up. Prolonged exposure to cold can lead to loss of consciousness or a serious allergic reaction known as anaphylaxis. Other skin problems can also occur in PLAID. A small number of affected individuals develop a blistering rash on the tip of their nose, ears, and fingers shortly after birth. The rash usually heals on its own in infancy, although in rare cases, it worsens over time. After the initial rash goes away, a different rash sometimes develops on the torso and limbs later in life. This rash, called a granuloma, can affect small patches of skin or be widespread. In people with PLAID, the granulomas do not occur in warm regions of the body, such as the armpits and other skin folds. In many people with PLAID, immune system function is reduced, leading to recurrent infections such as frequent colds, ear infections, or bouts of pneumonia. The infections are likely related to lower-than-normal levels of special proteins called antibodies or immunoglobulins, particularly immunoglobulin M (IgM) or immunoglobulin G (IgG). Antibodies attach to specific foreign particles and germs, marking them for destruction. The number of immune system cells called natural killer (NK) cells may also be reduced. Autoimmune disorders, which occur when the immune system malfunctions and attacks the bodys own tissues and organs, can also occur. Autoimmune disorders associated with PLAID include autoimmune thyroiditis and vitiligo. Autoimmune thyroiditis results from damage to the butterfly-shaped, hormone-producing gland in the lower neck (the thyroid). Vitiligo is caused by attacks on the pigment cells in the skin, resulting in a patchy loss of skin coloration. Most people with PLAID have abnormal antibodies called autoantibodies in their blood. One such antibody common in people with PLAID is known as antinuclear antibody (ANA). Autoantibodies attach to normal proteins and can trigger an immune attack against the bodys own tissues. However, not everyone with these abnormal antibodies has an autoimmune disease.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"as a Newborn and as an Infant","SourceID__c":"ORPHA:300359","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0013766","ORPHANET_ID__c":"ORPHA:300359","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Deficiencia de anticuerpos asociada a plcg2 y desregulación inmunológica","Spanish_Description_Source__c":"ORPHA:300359","Spanish_Description__c":"La deficiencia de anticuerpos asociada a PLCG2 y desregulación inmunitaria es una inmunodeficiencia, hereditaria y poco frecuente, con afectación cutánea. Está caracterizada por urticaria por frío de inicio temprano por exposición generalizada al aire frío o enfriamiento por evaporación y no por el contacto con objetos fríos. Con frecuencia, hay anomalías inmunológicas adicionales presentes: deficiencia de anticuerpos, infecciones recurrentes, enfermedad autoinmune y enfermedad alérgica sintomática.","Spanish_Disease_Name__c":"deficiencia de anticuerpos asociada a plcg2 y desregulación inmunológica","Spanish_GARD_Synonym__c":"facu; plaid; urticaria familiar por frío atípica; urticaria familiar por frío con inmunodeficiencia común variable","Category_Linearization__c":"ORPHA:98023","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":"PLCG2-associated antibody deficiency and immune dysregulation (PLAID) is an immune system disorder characterized by an allergic reaction to cold temperatures. Other immune system problems can also occur. The hallmark feature of PLAID is the development of a red, itchy rash (hives) when the skin is exposed to cool temperatures, which is known as cold urticaria. In PLAID, the hives typically develop in response to evaporative cooling, such as when a cool breeze or air conditioning blows on damp or sweaty skin. Being in a cold swimming pool can also trigger hives. In contrast, people with PLAID do not have a reaction when they touch a cold object, like an ice cube. (The ice cube test is a common test for a cold allergy; it triggers a reaction in people with other forms of cold urticaria, which usually begin later in life than PLAID.) However, some people with PLAID do experience a burning sensation in their throats when they eat cold foods, like ice cream. In PLAID, the hives go away once the skin warms up. Prolonged exposure to cold can lead to loss of consciousness or a serious allergic reaction known as anaphylaxis. Other skin problems can also occur in PLAID. A small number of affected individuals develop a blistering rash on the tip of their nose, ears, and fingers shortly after birth. The rash usually heals on its own in infancy, although in rare cases, it worsens over time. After the initial rash goes away, a different rash sometimes develops on the torso and limbs later in life. This rash, called a granuloma, can affect small patches of skin or be widespread. In people with PLAID, the granulomas do not occur in warm regions of the body, such as the armpits and other skin folds. In many people with PLAID, immune system function is reduced, leading to recurrent infections such as frequent colds, ear infections, or bouts of pneumonia. The infections are likely related to lower-than-normal levels of special proteins called antibodies or immunoglobulins, particularly immunoglobulin M (IgM) or immunoglobulin G (IgG). Antibodies attach to specific foreign particles and germs, marking them for destruction. The number of immune system cells called natural killer (NK) cells may also be reduced. Autoimmune disorders, which occur when the immune system malfunctions and attacks the bodys own tissues and organs, can also occur. Autoimmune disorders associated with PLAID include autoimmune thyroiditis and vitiligo. Autoimmune thyroiditis results from damage to the butterfly-shaped, hormone-producing gland in the lower neck (the thyroid). Vitiligo is caused by attacks on the pigment cells in the skin, resulting in a patchy loss of skin coloration. Most people with PLAID have abnormal antibodies called autoantibodies in their blood. One such antibody common in people with PLAID is known as antinuclear antibody (ANA). Autoantibodies attach to normal proteins and can trigger an immune attack against the bodys own tissues. However, not everyone with these abnormal antibodies has an autoimmune disease.","Curated_Disease_Description_Source__c":"ORPHA:300359","GARD_Synonym__c":"antibody deficiency and immune dysregulation, plcg2-associated; facu; familial atypical cold urticaria; familial cold autoinflammatory syndrome caused by mutation in plcg2; familial cold autoinflammatory syndrome type 3; familial cold urticaria with common variable immunodeficiency; fcas3; plaid; plcg2 familial cold autoinflammatory syndrome; plcg2-associated antibody deficiency and immune dysregulation","Name":"Familial cold autoinflammatory syndrome 3","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Autoinflammatory Alliance","Website__c":"https://www.autoinflammatory.org/"},{"Account_Name__c":"The International Foundation for Autoimmune & Autoinflammatory Arthritis","Website__c":"https://www.aiarthritis.org/"}],"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":"Rheumatology","Tag_Category__c":"Specialist"},{"Tag_Name__c":"Immunology","Tag_Category__c":"Specialist"},{"Tag_Name__c":"Dermatology","Tag_Category__c":"Account;Disease Category;Specialist","category_description":"Skin diseases, or integumentary system diseases, affect the skin, hair, nails, sweat glands, or oil glands.","curated_tag_name":"Skin diseases"},{"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":"Infancy","Provided_By__c":"ORPHA:300359"},{"Age_At_Onset__c":"Neonatal","Provided_By__c":"ORPHA:300359"}],"External_Identifier_Disease__c":[{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C3280914","Source__c":"C3280914","Xref__c":"C3280914"},{"URL__c":"https://www.orpha.net/en/disease/detail/300359","Source__c":"C3280914; MONDO:0013766","Xref__c":"ORPHA:300359"},{"URL__c":"https://www.omim.org/entry/614468","Source__c":"C3280914; MONDO:0013766; ORPHA:300359","Xref__c":"OMIM:614468"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=482544","Source__c":"C3280914","Xref__c":"MEDGEN:482544"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0090064","Source__c":"MONDO:0013766","Xref__c":"DOID:0090064"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0013766","Source__c":"GARD:0017369","Xref__c":"MONDO:0013766"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"PLCG2","GHR_URL__c":"https://medlineplus.gov/genetics/gene/plcg2","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal dominant"],"GARD_Disease_Feature__c":[{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Presyncope is a state of lightheadedness, muscular weakness, blurred vision, and feeling faint. Presyncope is most often cardiovascular in cause.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0031972","HPO_Name__c":"Presyncope","Feature_System__c":"Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A fungal infection of the toenails or fingernails that tends to cause the nails to thicken, discolor, disfigure, and split.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012203","HPO_Name__c":"Onychomycosis","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A chronic, autoimmune type of thyroiditis associated with hypothyroidism.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000872","HPO_Synonym__c":"Chronic lymphocytic thyroiditis; Hashimoto's thyroiditis","HPO_Name__c":"Hashimoto thyroiditis","Feature_System__c":"Endocrine System; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000989","HPO_Synonym__c":"Itching; Itchy skin; Skin itching","HPO_Name__c":"Pruritus","Feature_System__c":"Skin System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Urticaria may be caused by cold temperatures.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0410135","HPO_Name__c":"Cold urticaria","Feature_System__c":"Skin System; Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa and submucosal tissues of the skin of the face, normally around the mouth, and the mucosa of the mouth and/or throat, as well as the tongue during a period of minutes to several hours. The swelling can also occur elsewhere, typically in the hands. Angioedema is similar to urticaria, but the swelling is subcutaneous rather than on the epidermis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0100665","HPO_Synonym__c":"Angioneurotic edema; Angiooedema; Quincke edema","HPO_Name__c":"Angioedema","Feature_System__c":"Skin System; Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0010783","HPO_Synonym__c":"Redness of skin or mucous membrane","HPO_Name__c":"Erythema","Feature_System__c":"Skin System; Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002099","HPO_Synonym__c":"Asthma; Bronchial asthma","HPO_Name__c":"Asthma","Feature_System__c":"Respiratory system; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An increased susceptibility to infections involving both the paranasal sinuses and the lungs, as manifested by a history of recurrent sinopulmonary infections.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0005425","HPO_Synonym__c":"Chronic sinopulmonary infection; Recurrent sinus and lung infections","HPO_Name__c":"Recurrent sinopulmonary infections","Feature_System__c":"Respiratory system; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001045","HPO_Synonym__c":"Blotchy loss of skin color","HPO_Name__c":"Vitiligo","Feature_System__c":"Skin System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"The presence of autoantibodies in the serum that react against nuclei or nuclear components.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003493","HPO_Synonym__c":"Antinuclear antibodies; Antinuclear antibody positive; Elevated antinuclear antibody; Serum antinuclear antibody","HPO_Name__c":"Antinuclear antibody positivity","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Occasional (5-29%)","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":"OMIM:614468","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An exaggerated whealing tendency when the skin is stroked, that is, formation of red, itchy bumps and lines on the skin as a result of pressure on the skin (for instance, stroking the skin with a pen or tongue depressor).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011971","HPO_Synonym__c":"Dermatographism; Dermographism; Skin writing","HPO_Name__c":"Dermatographic urticaria","Feature_System__c":"Skin System; Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"It is characterized by one or more symptoms including sneezing, itching, nasal congestion, and rhinorrhea.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003193","HPO_Synonym__c":"Hay fever; Hayfever","HPO_Name__c":"Allergic rhinitis","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:614468","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An allergy is an immune response or reaction to substances that are usually not harmful.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012393","HPO_Synonym__c":"Allergy","HPO_Name__c":"Allergy","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics"],"Disease Category":["Genetics","Dermatology"],"Specialist":["Genetics","Rheumatology","Immunology","Dermatology","Pediatrics"],"Account":["Dermatology","Primary Immune Deficiencies"]},"synonyms":["antibody deficiency and immune dysregulation, plcg2-associated"," facu"," familial atypical cold urticaria"," familial cold autoinflammatory syndrome caused by mutation in plcg2"," familial cold autoinflammatory syndrome type 3"," familial cold urticaria with common variable immunodeficiency"," fcas3"," plaid"," plcg2 familial cold autoinflammatory syndrome"," plcg2-associated antibody deficiency and immune dysregulation"]}