Nuclear factor kappaB essential modulator-deficient child with immunodeficiency yet without anhidrotic ectodermal...

Area of Science:

• Genetics
• Immunology
• Molecular Biology

Background:

• Amorphic mutations in the Nuclear Factor kappaB Essential Modulator (NEMO) gene cause Incontinentia Pigmenti, typically lethal in males.
• Hypomorphic NEMO mutations are associated with ectodermal dysplasia (EDA) and immunodeficiency in male patients.

Observation:

• A male child presented with severe immunodeficiency, including Mycobacterium avium disease, recurrent bacterial infections, and autoimmune complications, but notably lacked signs of EDA.
• Immunologic evaluation revealed impaired interferon-gamma (IFN-γ) production and a hyper-IgM phenotype.

Findings:

• Genetic analysis identified a novel hypomorphic NEMO mutation (110-111insC in exon 2) in the patient.
• Despite extensive treatment, the patient experienced chronic illness and ultimately fatal herpes simplex virus 1 encephalitis.

Implications:

• This case expands the clinical spectrum of NEMO mutations, demonstrating that immunodeficiency without EDA can occur in hemizygous males.
• Testing for NEMO gene mutations should be considered in male children with severe, unexplained immunodeficiency, irrespective of the presence or absence of EDA.