Recurrent rhinovirus infections in a child with inherited MDA5 deficiency

Lamborn, Ian T.; Jing, Huie; Zhang, Yu; Drutman, Scott B.; Abbott, Jordan K.; Munir, Shirin; Bade, Sangeeta; Murdock, Heardley M.; Santos, Celia P.; Brock, Linda G.; Masutani, Evan; Fordjour, Emmanuel Y.; McElwee, Joshua J.; Hughes, Jason D.; Nichols, Dave P.; Belkadi, Aziz; Oler, Andrew J.; Happel, Corinne S.; Matthews, Helen F.; Abel, Laurent; Collins, Peter L.; Subbarao, Kanta; Gelfand, Erwin W.; Ciancanelli, Michael J.; Casanova, Jean-Laurent; Su, Helen C.

We have intensively studied a 5-yr-old child who had recurrent viral respiratory infections requiring frequent hospitalizations ( Fig. 1 A; see Clinical description in Materials and methods). At birth, she had a suspected congenital infection, although prenatal infectious screening was normal. At 40 d of age, she had respiratory failure from concurrent HRV/ enterovirus and influenza B virus infections, which required mechanical ventilation, including extracorporeal membrane oxygenation. Since then, she has been repeatedly infected with HRV/enteroviruses detected in nasopharyngeal secre-tions and respiratory distress. She had two more episodes of influenza A (H3 subtype) and adenovirus, infections with three different coronaviruses (OC43, NL63, and HKU1), and one episode each of RSV and parainfluenza virus type 4. Tests for human metapneumovirus were negative. She continues to require supplemental oxygen and had ground glass opacities, but no bronchiectasis on chest-computed tomography. She has had bacterial superinfections of the respiratory tract, but no opportunistic or chronic systemic virus infection, including EBV or CMV. Although she initially had low serum immunoglobulin levels and lymphopenia (effecting T, NK, and B cell subsets) , these all normalized between 3 and 4 yr of age. Replacement immunoglobulin therapy, which started at 70 d of age when she was severely ill, was discontinued, and she has since responded with functional antibodies to tetanus, diphtheria, and Haemophilus influenzae vaccines. An older brother died of an unknown infectious cause at age one month in a refugee camp. The patient's parents and two other older siblings were healthy.