Caspase 8 Deficiency

A number sign (#) is used with this entry because of evidence that caspase-8 deficiency is caused by homozygous mutation in the CASP8 gene (601763) on chromosome 2q33. One such family has been reported.

Description

Caspase 8 deficiency is a syndrome of lymphadenopathy and splenomegaly, marginal elevation of 'double-negative T cells' (DNT; T-cell receptor alpha/beta+, CD4-/CD8-), defective FAS-induced apoptosis, and defective T-, B-, and natural killer (NK)-cell activation, with recurrent bacterial and viral infections (summary by Madkaikar et al., 2011).

Clinical Features

Chun et al. (2002) reported 2 sibs, a 12-year-old female and an 11-year-old male, born of consanguineous parents, who presented with lymphadenopathy and splenomegaly associated with an immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections. Both sibs showed poor responses to immunization. The affected sibs had 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 well, although their peripheral blood lymphocytes showed partial defects in CD95-mediated apoptosis.

Molecular Genetics

In 2 affected sibs from a consanguineous family with caspase-8 deficiency, Chun et al. (2002) identified a homozygous mutation in the CASP8 gene (601763.0001). The unaffected mother, father, and sister were heterozygous for the mutation.

Nomenclature

Puck and Straus (2004) referred to caspase 8 deficiency as autoimmune lymphoproliferative syndrome type IIB; see 601859. In review articles, Teachey et al. (2009) stated that caspase 8 deficiency is distinct from ALPS and Madkaikar et al. (2011) stated that caspase 8 deficiency is an 'ALPS-related' disorder.