Deficiencies in IKBKG or NFKBIA result in a defect in NF-kappaB mediated immunity, which predisposes the patient to recurrent infections, which can be life-threatening.
Chromosome: Xq28
Gene: IKBKG (inhibitor of nuclear factor kappa B kinase subunit gamma)
Also known as: NEMO
Function: inhibitor of kappa-B kinase complex
Inheritance: X-linked
Chromosome: 14q13.2
Gene: NFKBIA (NFKB inhibitor alpha)
Also known as: IKBA
Function: inhibits NF-kappa-B/REL complexes
Mutations are present in ectodermal dysplasia anhidrotic with T-cell immunodeficiency.
Inheritance: autosomal
Clinical Features:
(1) recurrent bacterial infections that may be noninvasive or invasive (meningitis, encephalitis, sepsis, osteomyelitis, infectious diarrhea, pneumonia, ENT infections, etc)
(2) systemic signs of inflammation are weak or delayed
(3) opportunistic infections with viruses, parasites and/or fungi
(4) variable hypogammaglobulinemia
Bacterial pathogens to which the patient may be susceptible:
(1) Streptococcus pneumoniae
(2) Pseudomonas aeruginosa
(3) Staphylococcus aureus
(4) Hemophilus influenzae
(5) Salmonella species
(6) Klebsiella pneumoniae
(7) Serratia marcescens
(8) environmental mycobacteria
Other pathogens:
(1) Candida albicans
(2) Pneumocystis jirovecii
(3) Herpes simplex virus
(4) cytomegalovirus
(5) adenovirus
Aggressive management during childhood can be effective:
(1) antibiotic prophylaxis with early, empiric antibiotic therapy
(2) IgG infusion (IV or subcutaneous)
(3) vaccination if functional B-cell immunity
