Clinical Manifestations and Genetic Analysis of 17 Patients with Autosomal Dominant Hyper-IgE Syndrome in Mainland China: New Reports and a Literature Review.

PURPOSE: Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare complicated primary immunodeficiency disease (PID). Signal transducer and activator of transcription 3 (STAT3) gene mutation is found to cause AD-HIES. The distribution of AD-HIES patients with STAT3 deficiency in the Chinese population is not clear. Herein, we retrospectively report 17 AD-HIES patients with STAT3 deficiency and demonstrate their clinical, immunological, and genetic features.

METHODS

Patients' clinical data were collected from their medical records. Routine laboratory testing results included lymphocyte subset analysis and immunoglobulin quantification. STAT3 mutations were investigated by sequencing of genomic DNA.

RESULTS

Among 575 patients with PID, 28 (4.87%) were clinically diagnosed as HIES. Among them, 17 (2.96%) were confirmed as STAT3 mutant AD-HIES. The ratio of male to female patients was 8:9. All of the 17 patients had NIH scores over 40 points. The mean ages at onset and diagnosis were 1.05 and 10.35 years, respectively. Three patients (17.65%, 3/17) died with a mean age of 13.33 years. Eczema, recurrent skin infection, and respiratory tract infection were the most common clinical symptoms and are present in all of the 17 patients in this study. Six patients (37.5%, 6/16) suffered complication from BCG vaccination. Noninfection symptoms are characteristic facial features in 17 patients (100%, 17/17), retention of primary teeth in 10 patients (90.91%, 10/11), and abnormal bone fractures in 7 patients (41.18%, 7/17). Eleven types of STAT3 mutations were identified in 17 patients, including 1 novel mutation.

CONCLUSIONS

We here retrospectively report the largest Chinese cohort of AD-HIES patients with STAT3 mutation. Unique features, when compared to existing literature reports, include (1) later age of diagnosis, (2) significantly higher rate of BCG complications, and (3) lower rate of candidiasis and chronic otitis media.