Immundeficiency 44 D84.9

Immunodeficiency 44, also known as IMD44, is an autosomal recessive primary immunodeficiency characterized by increased susceptibility to viral infections and, in some patients, a multisystemic response to vaccination. Affected individuals appear to have defects in mitochondrial fission and fusion (abstract by Shahni et al. 2015).

The clinical picture of immunodeficiency 44 is apparently caused by homozygous mutations in the STAT2 gene (chromosome 12q13). Immunoblotting of selected interferon-stimulated genes in proband fibroblasts indicates blockage of signal transduction with ISGF3 .

Hambleton et al (2013) reported on a 5-year-old boy born to consanguineous parents with a history of measles that developed 6 days after routine measles/mumps/rubella (MMR) vaccination at 18 months of age. One sibling later died suddenly in the course of a 2-day febrile illness with features of viral infection. Extended kinship analysis identified 3 additional patients with variable manifestations of a similar immunodeficiency: 2 children had a history of severe viral illness, including 1 who developed encephalitis after MMR vaccination, but her homozygous mother's recent history of infection was unremarkable. However, other viral illnesses in these patients were generally mild: 3 of the 5 had unremarkable varicella and 1 had a primary herpes simplex virus infection that manifested as gingivostomatitis but not encephalitis. The inheritance pattern of IMD44 in the family was consistent with an autosomal recessive inheritance.

Laboratory studies of the proband did not indicate a B- or T-cell immunodeficiency. The patient's fibroblasts showed increased selective susceptibility to viral infections resulting from a failure of the type 1 interferon response to alpha-interferon compared to controls.

1. Hambleton S et al (2013) STAT2 deficiency and susceptibility to viral illness in humans. Proc Nat Acad Sci 110: 3053-3058
2. Shahni R et al (2015) Signal transducer and activator of transcription 2 deficiency is a novel disorder of mitochondrial fission. Brain 138: 2834-2846