Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is an X-linked inborn error of immunity caused by hypomorphic mutations in the IKBKG gene, disrupting NF-κB signaling. Its clinical presentation is heterogeneous and includes severe bacterial, mycobacterial, viral, and fungal infections, along with classic ectodermal features such as hypohidrosis, hypotrichosis, and hypodontia.
We report a 1-year-4-month-old Peruvian male with recurrent severe infections since the first month of life, including oral candidiasis, complicated pneumonia, central nervous system tuberculous granuloma, sepsis, and cytomegalovirus viremia. Physical examination revealed facial dysmorphism, sparse hair, xerosis, hypohidrosis, and conical teeth. Immunological evaluation showed hypogammaglobulinemia (IgG 435 mg/dL) with normal IgA and IgM levels, and unremarkable T, B, and natural killer cell subsets. Monthly intravenous immunoglobulin therapy and antimicrobial prophylaxis were initiated. A primary immunodeficiency gene panel revealed only variants of uncertain significance (VUS), and exome sequencing failed to identify a candidate gene. Ultimately, targeted Sanger sequencing identified a VUS in IKBKG [c.522_527dup; p.R175_A176dup], located in a functionally critical region of the NEMO protein.
The clinical phenotype and genetic findings support a presumptive diagnosis of EDA-ID. The localization of the VUS suggests a potential structural disruption, impairing IKK complex oligomerization and NF-κB activation, affecting both innate and adaptive immunity. This may represent the first clinically well-documented suspected case of EDA-ID in Peru and South America. The case underscores the importance of early clinical recognition and stepwise molecular diagnostics in immunodeficiencies and highlights the regional need for functional and familial studies to confirm the pathogenicity of IKBKG variants and improve diagnosis.
