Wiskott-Aldrich syndrome - Patients develop thrombocytopenia which is often present at birth. The mean platelet volume is decreased (3.8-5.0 fl) compared to normal individuals (7.1-10.5 fl). Patients commonly present with bloody diarrhea, bruising, petechiae, purpura, and bleeding from the circumcision site. Splenectomy can often improve thrombocytopenia in patients but increases the risk of sepsis with encapsulated bacteria. In addition, patients may also develop autoimmune thrombocytopenia (which is not responsive to splenectomy).
Autoimmune Lymphoproliferative Syndrome (ALPS) - This disease is characterized by defective activation induced cell death that leads to uncontrolled lymphoproliferation. Patients develop hepatosplenomegaly, adenopathy, and autoimmune cytopenias (autoimmune hemolytic anemia, ITP, autoimmune neutropenia).
CVID - Approximately 25% ofpatients develop autoimmune disease. Autoimmune hemolytic anemia and ITP are the most frequently reported conditions. ITP precedes the diagnosis of CVID in approximately 10% of patients.
IPEX syndrome - Approximately one-half of patients develop autoimmune cytopenias including ITP, coombs positive hemolytic anemia, and autoimmune neutropenia.
AID deficiency - Patients develop autoimmune manifestations at high frequency (approximately 25%). These include ITP, hemolytic anemia, and autoimmune hepatitis.
Cartilage Hair Hypoplasia - Patients may develop autoimmune manifestations such as ITP, hemolytic anemia, juvenile idiopathic arthritis, and autoimmune enteropathy.
Purine Nucleoside Phosphorylase (PNP) deficiency - Patients develop a number of autoimmune manifestations including ITP, hemolytic anemia, and autoimmune neutropenia. Less common manifestations include SLE and CNS vasculitis.
Fanconi pancytopenia - This is an AR inherited bone marrow failure syndrome that results in anemia and thrombocytopenia. Neutropenia secondary to marrow failure occurs in 95% of patients (T and B cell immunity is normal). Additional features include short stature, radial hypoplasia, microcephaly, renal and genital anomalies, skin hyperpigmentation, mental retardation, and characteristic facial features.
Transcobalamin II deficiency - Patients develop macrocytic anemia, thrombocytopenia, and neutropenia. Immunologic abnormalities include lymphopenia, hypogammaglobulinemia, and impaired specific antibody responses. Replacement therapy with hydroxycobalamin can reverse the clinical manifestations of this disease.
Kabuki syndrome - Patients may develop ITP and autoimmune hemolytic anemia.
Cernunnos deficiency - ITP and hemolytic anemia and have been reported been reported in this disease.
CTLA4 Deficiency - patients develop multi-organ autoimmune manifestations including inflammatory bowel disease,autoimmune cytopenia, psoriasis, and thyroid disease. Patients also develop splenomegaly, hepatomegaly, bronchiectasis, GLILD, and generalized lymphadenopathy.
LRBA Deficiency - patients develop multi-organ autoimmune manifestations including inflammatory bowel disease,autoimmune cytopenia, psoriasis, and thyroid disease. Patients also develop splenomegaly, hepatomegaly, bronchiectasis, GLILD, and generalized lymphadenopathy.
PIK3CD Gain of Function - patients develop autoimmune manifestations including inflammatory bowel disease, autoimmune cytopenia, and autoimmune primary sclerosing cholangitis. Patients may also develop EBV/CMV induced lymphoproliferation, hepatosplenomegaly and malignancy (lymphoma).
STAT3 Gain of Function - patients develop multi-organ autoimmune manifestations including autoimmune enteropathy autoimmune cytopenia, type I diabetes, and interstitial lung disease.