IMDDHH: A Contribution to the Understanding of the Disease

Abstract

Inborn Errors of Immunity (IEI) is an extremely rare group of heterogenous disorders which are characterized by predisposition to severe unusual and recurrent infections, severe allergies, features suggestive of autoimmune conditions and sometimes malignancies. We report a two-year-old female child presented to our emergency department with complaints of a history of recurrent respiratory infections, recurrent skin infections and a recent history of purulent discharge from both ears. Clinical examination revealed acute otitis media, pneumonia, multiple healed skin lesions associated with soft non-tender hepatomegaly and normal cardiac findings. Elevated hepatic transaminases and hypogammaglobulinemia suggested the possibility of an inborn error of immunity. A whole exome sequencing study performed on the patient established a diagnosis of IMDDHH (Immunodeficiency, Developmental Delay, and Hypohomosyteinemia) by revealing a missense mutation in the NFE2L2 gene of chromosome 2q31. Diagnosing such conditions with inborn errors of immunity requires a high index of suspicion combined with a comprehensive knowledge of the structure and function of both innate and adaptive immune systems. Recurrent skin and respiratory infections in a growing child belonging to a low-and-middle-income country like India is a common clinical scenario encountered frequently in pediatric clinic practice and is often ignored after attributing it to poor hygienic conditions. However, with careful history taking and examination, a sub-group of such patients may be isolated with a high probability of an underlying IEI, which can later be confirmed by genetic work-up.