PURPOSE OF THE STUDY.
The goal of this study was to elucidate viral resistance despite immunodeficiency in a rare congenital disorder of glycosylation type IIb.
The study subjects were 2 siblings presenting with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemia but limited clinical evidence of recurrent severe infections.
An 11-year-old boy and 6-year-old girl, first and third children, born to a young, healthy, non-consanguineous couple were evaluated. They are characterized by dysmorphic features, hypotonia, seizures, global developmental delay, cerebral atrophy, optic nerve atrophy, hearing loss, and recurrent bone fractures.
The siblings had normal or increased numbers of B cells in peripheral blood but severe hypogammaglobulinemia (317 mg/dL and 142 mg/dL) with significantly shortened half-life for IgG (6 days). The patients had normal specific antibody response to polysaccharide proteins, conjugated proteins, and polysaccharide antigens but did not respond to live virus vaccines such as measles-mumps-rubella (vaccine) or varicella, which are viruses with glycosylated envelopes. These patients did not have altered susceptibility to adenovirus or parvovirus 1, which are nonenvelope viruses, or to vaccinia virus, which is an envelope virus. In contrast, the patients did have markedly reduced susceptibility to infection with HIV and influenza viruses, which are glycosylation-dependent envelope viruses.
These data seem to suggest that altered glycosylation may modify the susceptibility to infection with viruses that must undergo protein glycosylation to complete their infection cycle.
This study helps us to continue to expand our understanding of genetically determined permutations of host defense that could aid in explaining these unusual and unanticipated clinical presentations.
- Copyright © 2014 by the American Academy of Pediatrics