However, it is not unusual to find patients with clinical manifestations characteristic of APS but with persistently negative aPL tests including aCL and aβ2GPI; IgG and IgM, detected by enzyme linked immunosorbent assay (ELISA); and LA detected by clotting assays according to the guidelines of the International Society on Thrombosis and Haemostasis in daily clinical practice. This evidence concerns the gene ACLY and autoimmune polyendocrinopathy.