Novel NF-kappa B Inhibitor Alpha Gain-of-Function Variant in an Infant with Lymphocytosis and Recurrent Serratia Bacteremia.

In this letter, we describe a patient who presented shortly after birth with recurrent infections, lymphocytosis, and congenital anomalies and was found to have a novel, private NF-kappa B Inhibitor Alpha ( I NFKBIA i ) variant, characterized in vitro to be a gain-of-function (GOF) allele. Yet, similar to previously reported patients with EDA-ID, we observed complications with HSCT including falling/mixed chimerism, and he eventually succumbed to his disease with infection causing worsening respiratory distress and parental desire for patient comfort. Complications from transplant were significant with over 50% of the 11 transplanted patients dying post-transplant, while four of the living transplanted patients remained on prophylaxis. (A) Time-course of TIL-1 -stimulated (right) SV40 fibroblasts from 2 controls, patient (NFKBIA D31N/WT), and NEMO deficient patient (NEMO-/-) with immunoblotting for phospho-IKK (p-IKK), IKK , p-I B , I B and GAPDH. [Extracted from the article]