Autoimmune Lymphoproliferative Syndrome With Recurrent Viral Infections

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

CASP8, FAS, COL1A1, NRAS, FASLG, COL5A1, COL5A2, CASP10, FADD, FN1, TLR4, TNFRSF1A, RIPK1, RIPK3

Drugs

Allogeneic multi-virus specific T lymphocytes targeting BK virus, cytomegalovirus, human herpesvirus-6, Epstein Barr virus and adenovirus, haematopoietic stem cells and blood progenitors umbilical cord-derived expanded with (1R, 4R)-N1-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)cyclohexane-1,4-diamine dihydrobromide dihydrate

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A rare genetic disorder characterized by lymphadenopathy and/or splenomegaly and recurrent infections due to herpes viruses.

Epidemiology

Prevalence of this disorder is not known. It is extremely rare with four individuals in one family identified to date.

Clinical description

Development is reported to be normal in affected patients. Clinical signs include lymphadenopathy and splenomegaly, and development of recurrent sinopulmonary and significant mucocutaneous infections with the Herpes zoster and Herpes simplex viruses. Patients are also poorly responsive to immunization and seem to benefit from IVIG supplementation.

Etiology

The disorder is caused by germline homozygous mutations in the CASP8 gene (2q33-q34) involved in the execution phase of cell apoptosis. Carriers with a normal copy of the gene are asymptomatic.

Diagnostic methods

Biologically, autoimmune lymphoproliferative syndrome with recurrent viral infections is characterized by slightly elevated double-negative T cells (DNTs), and defective Fas-mediated apoptosis of B, T, and NK lymphocytes.

Genetic counseling

The pattern of inheritance appears to be autosomal recessive.