Recurrent Infections and EGID in CARMIL2 Deficiency

CARMIL2 is a protein required for T cell activation, specifically for CD28 and CARMA-1/PKC coupling and NF-kB signaling. CARMIL2 deficiency has pleiotropic presentations, which can include recurrent viral and mucocutaneous infections and very early onset inflammatory bowel disease (VEO-IBD). Here, we present a 6-year-old Caucasian male with failure to thrive, recurrent infections, as well as eosinophil-associated gastrointestinal disorders (EGID). He was status post adenoidectomy x 3, bilateral myringotomy placement x 2, and tonsillectomy x 1, presented for recurrent ear infection. He had an unremarkable newborn period. The patient developed ear infections at 6 months old that would persist despite antibiotics and surgeries. No known family history, and parents were not known to be consanguineous. He had a perianal skin infection that persisted for 12 months, despite adequate treatment. Outside allergist performed an immune workup at 2 years old, which showed low titers to pneumococcal vaccine and low IgG. Never had any overwhelming systemic infections. Due to the persistence and reoccurrence of infections despite surgeries and antibiotics, a repeat immune workup was performed. B and T cell flow cytometry, dihydrorhodamine (DHR) test, and complement were normal. DTaP and pneumococcal vaccine titers showed adequate post-vaccine response. However, he had low IgG (367), low class-switched B cells, absent T cell proliferation to tetanus, lymphocytosis, and eosinophilia. Genetic testing showed compound heterozygous CARMIL2 deficiency. The patient also had bloating and abdominal pain, and endoscopy showed 16 eosinophils per high-powered field in the distal esophagus, as well as eosinophilic gastritis. Most patients with CARMIL2 deficiency were noted to have consanguinity, poor vaccine response, and skin infection. Although both parents’ genetic testing was found to have CARMIL2 mutations, the genomic variants were different, indicating less likelihood of consanguinity. Due to the rarity of CARMIL2 deficiency, specific treatment guidelines have yet to be established, but case reports noted improvement in disease process after immunoglobulin replacement. Our patient has started on immunoglobulin replacement and is on swallowed budesonide for his EGID.