Autoimmune lymphoproliferative syndrome type III: an indefinite disorder

Autoimmune Lymphoproliferative Syndrome (ALPS) is a childhood disorder characterized by chronic nonmalignant lymphoproliferation and autoimmunity. Although the pathogenesis is not fully understood, deficient Fas mediated apoptosis appears to be an important factor. This deficiency can be caused by a mutation of the APT1 gene (ALPS type Ia), of the FasL gene (ALPS type Ib), or of the Caspase-10 gene (ALPS type II). In one sub population of patients, no mutations have been identified as yet (ALPS type III). According to published data, the latter group is much smaller than the group of patients with ALPS type Ia. However, because of the variability of the clinical presentation and the absence of a known genetic defect, this disease is difficult to diagnose, the more so as few data have been reported on these patients. Thus, ALPS type III could be more common than believed until now. In this review we provide evidence for this hypothesis.