No abstract

Properdin deficiency was demonstrated in three generations of a large Swiss family. The concentration of circulating properdin in affected males was < 0.1 mg/l, indicating properdin deficiency type I. Two of the nine properdin-deficient males in the family had survived meningitis caused by Neisseria meningitidis serogroup B without sequel. Two point mutations were identified when the properdin gene in one of the properdin-deficient individuals was investigated by direct solid-phase sequencing of overlapping polymerase chain reaction (PCR) products. The critical mutation was found at base 2061 in exon 4, where the change of cytosine to thymine had generated the stop codon TGA. The other mutation was positioned at base 827 in intron 3. The stop codon in exon 4 was also demonstrated by standard dideoxy sequencing in three additional family members. The question was asked if genetic factors such as partial C4 deficiency and IgG allotypes could have influenced susceptibility to meningococcal disease in the family. No relationship was found between C4 phenotypes and infection. Interestingly, the two properdin-deficient males with meningitis differed from the other properdin-deficient persons in that they lacked the G2m(n) allotype, a marker known to be associated with poor antibody responses to T-independent antigens. This implies that the consequences of properdin deficiency might partly be determined by independent factors influencing the immune response.

A male infant with primary combined immunodeficiency, microcephaly with marked cerebellar hypoplasia, and growth failure of prenatal onset is presented. He developed progressive pancytopenia in the 3rd year of life and died at 42 months from disseminated aspergillosis. Laboratory studies and post mortem examination failed to reveal any known aetiology for his disorder. Hreidarsson et al. [3] previously described a syndrome of progressive pancytopenia with microcephaly, cerebellar hypoplasia and growth failure in three boys, with similar clinical and laboratory findings. Although extensive immunological investigations were not performed in those previous patients, recurrent infections in two of them are suggestive of immunodeficiency. In the light of the immunological findings in our patient, we propose that the condition of the four patients belongs to the same syndrome, which has to be considered as a primary combined immunodeficiency syndrome. This syndrome can be distinguished from the other known immunodeficiency syndromes by its associated characteristic features, namely microcephaly with cerebellar hypoplasia, growth failure of prenatal onset and progressive pancytopenia.

Cefepime and ceftazidime are equally safe and efficacious treatment for pyelonephritis in pediatric patients.