Autosomal recessive IRAK-4 and myeloid differentiation factor 88 deficiencies were reported in 2003 and 2008, respectively, conferring predisposition to pyogenic bacterial infections, and autosomal recessive UNC93B1 and autosomal dominant TLR3 deficiencies were reported in 2006 and 2007, respectively, conferring predisposition to herpes simplex encephalitis.
Finally, mutations in UNC93B1 and TLR3 are associated with childhood herpes simplex encephalitis, which strikes only once in most patients, with almost no recorded cases of more than two bouts of this disease.
By contrast, disorders of IFN-alpha/beta and IFN-lambda production, caused by UNC93B1 and TLR3 mutations, confer predisposition to herpes simplex encephalitis (HSE) in otherwise healthy patients.