Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity☆
Section snippets
Methods
In six consanguineous families (Fig 1), 13 patients were suspected of having a primary immunodeficiency based on unusual, severe, recurrent infections (Table I) and eczematoid rashes. Laboratory screening demonstrated elevated serum IgE levels and pronounced eosinophilia (Table I). All patients >1 year old fulfilled the clinical triad of HIES consisting of recurrent skin abscesses, recurrent pneumonia, and elevated IgE levels. Detailed case reports of the families are published in the online
Genetics
The pedigrees of the six consanguineous families with AR-HIES are depicted in Figure 1. Four male and nine female patients were offspring of consanguineous matings; affected subjects were seen in only one generation of each family. Thus, the inheritance pattern is most consistent with an autosomal-recessive mode. Though not known to be related to each other, five families were from Turkey. Therefore, the origin of these families is of genetic interest. Figure 1 shows that families 2, 3, and 5
Discussion
We have defined a novel autosomal-recessive variant of HIES. AR-HIES can be separated from AD-HIES by four major criteria, and therefore represents a distinct disease entity. First, the inheritance pattern of HIES in the six consanguineous families is very likely to be autosomal-recessive. Second, AR-HIES has no connective tissue features. AR-HIES appears to be limited to immune and inflammatory abnormalities. Third, AR-HIES has a particularly high incidence of CNS complications, with
Acknowledgements
We thank Dr M. Uhl for review and interpretation of radiographic data and Dr M. Schlesier for interpretation of immunologic data.
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Supplementary data associated with this article can be found at doi:10.1016/S0022-3476(03)00449-9.
Supported by a grant of the Deutsche Forschungsgemeinschaft GR-1617/2, and the fellowship of the Immune Deficiency Foundation, Towson, Maryland (to B. G.).