Autoimmune lymphoproliferative syndrome

Autoimmune lymphoproliferative syndrome is a form of lymphoproliferative disorder. It affects lymphocyte apoptosis.

ALPS results from mutations in the human genes, Fas and FasL, which are upstream effectors of the apoptotic pathway in cells.

Genetic Defect
The genetic defect for this syndrome is on the tumor necrosis factor receptor gene superfamily member (TNFRSF6), this is located on chromosome 10q24.1. This gene encodes for cell surface receptors involved in major apoptotic pathways for lymphocytes.

Mechanism of the Type IA
The mechanism of the Fas receptor version of this syndrome has to deal with the way Fas mediated apoptosis functions works. When the Fas Ligand bonds to three Fas receptors an apoptotic signal begins. However people with a genetic defect in their Fas receptors have some receptors that do not function properly. So even if two of the receptors are normal in the complex if one has a genetic defect then the Fas ligand will be either inhibited or will work less efficiently. Most genetic defects are merely a missence where one nucleotide is out of order, however other mutations include truncated forms which are excreted from the cell and when in the extracellular matrix can inhibit the ligands. This inefficacy of apoptosis in lymphocytes causes an increase in the number of lymphocytes in the body, including cells that are too old and less effective. This increase in the number of lymphocytes in the body causes an increase in the size of organs(http://www.patient.co.uk/doctor/Autoimmune-Lymphoproliferative-Syndrome.htm). The enlargement of organs can cause extra pressure on unaffected organs. When organs are enlarged they tend to work either too hard, or they do not work effectively. For example, when the liver is enlarged it tends to filter the blood ineffectively, causing the premature death of red blood cells. (http://www.patient.co.uk/doctor/Autoimmune-Lymphoproliferative-Syndrome.htm)

Presentation
Among the possible symptoms are splenomegaly and hepatomegaly.

Classification
Types include:
 * I - Canale-Smith syndrome
 * IA - Fas receptor (this form is the most common)
 * IB - Fas ligand
 * II
 * IIA - Caspase 10
 * IIB - Caspase 8
 * III - unknown
 * IV - Neuroblastoma RAS viral oncogene homolog