Autoimmune Lymphoproliferative Syndrome Type 2b D81.4

Autoimmunologic lymphoproliferative syndrome type 2b also known as caspase-8 deficiency is a rare, hereditary syndrome with lymphadenopathy and splenomegaly, a marginal increase in "double negative T cells" (DNT; T cell receptor alpha/beta+, CD4-/CD8-), defective FAS-induced apoptosis, and defective activation of T, B, and natural killer (NK) cells, with recurrent bacterial and viral infections (cf. Madkaikar et al. 2011).

Chun et al (2002) reported on two siblings, a 12-year-old girl and an 11-year-old boy born to consanguineous parents, who had lymphadenopathy and splenomegaly associated with immunodeficiency characterized by recurrent viral sinopulmonary infections and severe recurrent herpes simplex virus infections. Both siblings showed deficient vaccine responses. Evidence included defects in activation of T lymphocytes, B lymphocytes, and natural killer cells, and defective CD95-mediated apoptosis. The unaffected mother, father, and sister were clinically healthy, although their peripheral blood lymphocytes had partial defects in CD95-mediated apoptosis. Evidence included a homozygous mutation in the CASP8 gene (601763.0001). The unaffected mother, father, and sister were heterozygous for this mutation.

1. Chun HJ et al (2002) Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 419: 395-399.
2. Madkaikar M et al (2011) Advances in autoimmune lymphoproliferative syndromes. Europ J Haemat. 87: 1-9.
3. Puck JM et al (2004) Somatic mutations--not just for cancer anymore. New Eng J Med 351: 1388-1390.
4. Teachey DT et al (2009) Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS). Brit J Haemat 148: 205-216.