Current Perspectives in NEMO Deficiency Syndrome Management

Review Article

Abstract

NEMO deficiency syndrome, also known as X-linked hypohidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID), is a rare genetic disorder caused by mutations in the IKBKG gene encoding the NF-κB essential modulator (NEMO) protein. The condition primarily affects males and presents with a complex array of immune system abnormalities and ectodermal dysplasia. NEMO protein plays a crucial role in activating the NF-κB signaling pathway, which regulates various cellular processes including inflammation, immune response, and cell survival. The syndrome manifests with recurrent severe bacterial infections, particularly from Streptococcus pneumoniae and Staphylococcus aureus, along with characteristic features of ectodermal dysplasia including hypohidrosis, sparse hair, and dental anomalies. Immunological abnormalities encompass defects in both innate and adaptive immunity, affecting T cells, B cells, and natural killer cells. Diagnosis requires a comprehensive evaluation of clinical presentation, immunological parameters, and genetic testing. Treatment strategies primarily focus on preventing infections through immunoglobulin replacement therapy and prophylactic antibiotics. Hematopoietic stem cell transplantation may be considered for severe cases, although it does not address the ectodermal manifestations. The prognosis varies significantly depending on mutation severity and therapeutic intervention timing