The onset and diagnosis of severe combined immunodeficiency (SCID) typically occurs in infancy; however, in rare cases it is diagnosed in adulthood. A 24 year old male of normal intelligence presented with a seizure and was later diagnosed with disseminated aspergillosis with intracranial and pulmonary involvement. He had profound CD4 lymphopenia and subsequently developed hypogammaglobulinemia. He did not have history of recurrent infections and was previously in good health. Physical findings included dysmorphic facies, short stature, and microcephaly; thus radiosensitivity syndromes were considered.
Colony survival assay (CSA), Western blots, and DNA sequencing were performed.
CSA confirmed radiosensitivity. Western blots were performed for genes associated with double-stranded DNA breakage repair, and they were normal for: ATM (ataxia telangiectasia), NBS (Nijmegen breakage syndrome), FANCD2 (Fanconi anemia), APTX (ataxia-oculomotor apraxia syndrome), Artemis (Omenn syndrome and Athabascan-type severe combined immunodeficiency), PNPK, MRE11, and RAD50. Antibody for DNA ligase IV on fibroblast lysates prepared in RIPA buffer failed to detect DNA ligase IV. DNA sequencing of DNA ligase IV did not reveal mutations.
DNA ligase IV deficiency is an XCIND syndrome: X-ray-irradiation sensitivity, Cancer susceptibility, Immunodeficiency, Neurological abnormalities, and Double-strand DNA breakage. DNA ligase IV plays a major role in non-homologous end joining (NHEJ) and is also involved in physiological V(D)J rearrangement and class switching, thereby leading to immunodeficiency when a mutation occurs.
- AAAAI 2013 (69th)