Case 1
An 8-year-old male born at term had a history of unexplained neonatal
respiratory distress with a brief oxygen requirement. He had multiple
hospitalizations for recurrent pneumonia, recurrent otitis media,
sinusitis and wheezing. His evaluation included a normal chromosomal
microarray and sweat chloride test with an immunologic work up revealing
a nonspecific polyclonal gammopathy managed with prophylactic
antibiotics.
Computed tomography (CT) scan of his sinuses and chest at the age of 2
years revealed pansinusitis as well as multiple areas of mucus plugging,
atelectasis and tree in bud opacities. Repeat imaging at the age of 7
years showed progressive lung disease and development of bronchiectasis.
Bronchoscopy on two separate occasions demonstrated mucus plugging and
nodular mucosa with Moraxella catarrhalis and Hemophilus influenza
bacteria isolated from cultures. Measurements of nNO were obtained at
various points as part of an evaluation for PCD (Table ). PCD
genetic testing returned variants of unknown significance (VUS) in both
DNAH8 and DRC1 genes.
His symptoms of cough and rhinorrhea waxed and waned and were
uncharacteristic of PCD. Additionally, he had recurrent abdominal pain,
and abnormal stools. With the resolution of the previously reported
polyclonal gammopathy and gastrointestinal symptoms at the age of 6
years, repeat testing revealed normalization of nNO (Table ).
Whole exome sequencing was subsequently obtained and detected a
pathogenic mutation in the PIK3CD gene consistent with a diagnosis of
immunodeficiency.