Ku et al. (2007) described a 4.5-year-old boy born to unrelated Belgian parents in whom recurrent invasive pneumococcal disease (IPD) as the only clinical infectious manifestation of an inherited disorder in nuclear factor kappa-B (see 164011)-dependent immunity. The ... Ku et al. (2007) described a 4.5-year-old boy born to unrelated Belgian parents in whom recurrent invasive pneumococcal disease (IPD) as the only clinical infectious manifestation of an inherited disorder in nuclear factor kappa-B (see 164011)-dependent immunity. The boy had received all routine vaccinations with no adverse effect. In infancy, he developed mild but distinctive clinical features such as frontal bossing, hypodontia with conical incisors, and dry skin with normal sweating, consistent with a mild form of ectodermal dysplasia. At age 15 months, he was hospitalized for 4 days for persistent fever with buccal cellulitis, caused by Streptococcus pneumoniae serotype 33. He recovered completely after treatment with intravenous cefuroxime for 7 days. At age 22 months, the patient developed a left-sided limp with no fever, and mild periorbital cellulitis of the left eye caused by Streptococcus pneumoniae serotype 33. He was treated intravenously with an antibiotic for 7 days. With continuation of oral antibiotics, osteomyelitis of the left talus relapsed. After 6 weeks of intravenous antibiotic, followed by a 1-month course of oral antibiotic, he recovered from the osteomyelitis without sequelae. At age 23 months, he was vaccinated with heptavalent pneumococcal conjugate vaccine, with a second dose at age 25 months. After 15 months, he received a 23-valent pneumococcal vaccine. Despite these vaccinations, at age 2 years and 7 months, he presented with fever caused by infection with Streptococcus pneumoniae serotype 23. Three months later he developed arthritis of the left hip caused by Streptococcus pneumoniae serotype 23. Monthly prophylactic treatment with intravenous immunoglobulins was started when the patient was 3 years, 8 months old. Patient fibroblasts showed impaired responses to stimulation by both IL1-beta (147720) and TNF-alpha (191160). This and other responses suggested a defect downstream of the Toll/IL1R signaling pathway (see 603030).
In the Belgian patient described by them, Ku et al. (2007) found a 518C-G transversion in exon 4 of the NEMO gene, predicted to result in an arg173-to-gly (R173G) mutation (300248.0023). The mother was heterozygous for this mutation. ... In the Belgian patient described by them, Ku et al. (2007) found a 518C-G transversion in exon 4 of the NEMO gene, predicted to result in an arg173-to-gly (R173G) mutation (300248.0023). The mother was heterozygous for this mutation. Autosomal recessive IRAK4 deficiency (607676) and X-linked recessive NEMO deficiencies (e.g., 300291, 300584) are primary immunodeficiencies that affect NF-kappa-B-mediated immunity and cause a relatively broad susceptibility to infections. The patients described by Ku et al. (2007) displayed none of the other known infectious phenotypes associated with these disorders.