OLIGOGENIC HETEROZYGOUS MUTATIONS MANIFESTING AS COMBINED PRIMARY IMMUNODEFICIENCY

Abstract

Introduction Combined immunodeficiencies involving T and B lymphocytes have historically thought to be results of monogenic homozygous mutations. Our case illustrates a pediatric patient with oligogenic heterozygous mutations with phenotypical manifestations of combined humoral immunodeficiency. Case Description The patient is a 12-year-old Amish male who had severe recurrent lower respiratory tract infections during his first three years of life. During this time he was admitted to the hospital for respiratory infections on four occasions due to viral and bacterial etiologies, three of which required intubation for respiratory failure. The immunological evaluation revealed a persistent CD3+ T cell lymphopenia as well as a non-responsiveness to polysaccharide and conjugate pneumococcal vaccination. Over the subsequent years, he developed CD19+ B cell lymphopenia. Intravenous immunoglobulin replacement and trimethoprim/sulfamethoxazole prophylaxis were initiated which resolved all severe respiratory infections. Recently genetic testing was performed revealing heterozygous variants of three genes involved in immunodeficiency including purine nucleoside phosphorylase (PNP), IL17RA, and CARD9. Discussion Previously, combined immunodeficiency was thought to be monogenic in origin. This case represents the identification of suspected oligogenic heterozygous gene mutation variants believed to be the source of his combined immunodeficiency. With the advancement and affordable genetic evaluation, previously underestimated gene variants and mutations may play a significant role in the understanding of the etiologies of immunodeficiencies as illustrated by this case.