The symptoms returned when the supplements were stopped. == References ==
Other manifestations can affect the skin (hives), lungs (bronchiolitis obliterans), or kidneys (autoimmune glomerulonephritis and nephrotic syndrome). Another sign are cancers such as Hodgkin and non-Hodgkin lymphomas, which appear to be increased, possibly due to Epstein–Barr virus-encoded RNA-positivity. Some carcinomas may occur. Unaffected family members with genetic mutations are also at an increased risk of developing cancer. Genetics
This condition is usually caused by mutations in the FAS gene. Rarely cases due to mutations in other genes including the
FAS ligand gene have been reported. The disease is inherited in an autosomal dominant manner, but it shows incomplete penetrance with up to 40% of people with a FAS mutation not showing symptoms. Diagnosis
Diagnostic algorithm
The old diagnostic criteria for the illness included: Chronic non-malignant lymphoproliferation, elevated peripheral blood DNTs and defective in vitro Fas mediated apoptosis. The new criteria require chronic non-malignant lymphoproliferation (over six months lymphadenopathy and/or splenomegaly), elevated peripheral blood DNTs. A primary accessory in diagnosis is defective in vitro Fas mediated apoptosis and somatic or germline mutation in ALPS causative gene (FAS, FASL, CASP10). The secondary accessory in diagnosis are elevated biomarkers (plasma sFASL over 200 pg/ml, plasma IL-10 >20 pg/ml, plasma or serum vitamin B12 >1500 ng/L, Plasma IL-18 >500pg/ml) and immunohistochemical findings on biopsy consistent with ALPS as determined by an experienced hematopathologist. Another sign is autoimmune cytopenias and polyclonal hypergammaglobulinemia and a family history of ALPS or non-malignant lymphoproliferation.A definitive diagnosis is chronic non-malignant lymphoproliferation and/or elevated peripheral blood DNTs plus one primary accessory criterion.