Humoral immune defect with respiratory failure and skeletal abnormalities: A novel immune deficiency syndrome

Immune deficiency syndromes with skeletal abnormalities have been previously reported. Here we report a 16 year old boy who presented with arthrogryposis, hypogammaglobulinemia, failure to thrive, and severe respiratory failure. The child has a three year history of chronic cough and marked congestion. He was born with bilateral hip dysplasia, knee flexion contractures and club foot. He presented with a three year history of weight loss. CT scan showed cystic dilatation of bronchial airways. Immune studies revealed hypogammaglobulinemia (IgG 425,IgA 65, IgM 80) with low IgG subclasses (IgG1 266,IgG2 47, IgG3 79, IgG4<1). He failed to respond to tetanus and diptheria vaccinations, with an excellent response to HIB vaccine (>4000 fold increase). The patient had poor polysaccharide antigen responses, demonstrating protective antibody to only 2/12 pnemococcal serotypes. He had adequate numbers of T, B, NK cells (CD3 1680, CD19 470, CD56 650) with normal responses to mitogens (ConA,PHA,PWM) and antigens (tetanus,candida); TAP2 deficiency was excluded. The results demonstrate a new immune deficiency association involving arthrogryposis, failure to thrive, respiratory failure, and selective antibody production dysfunction.