Materials and Methods: The data were obtained from the Kuwait National Primary Immunodeficiency Disorders Registry during the period of 2004-2020.
Results: A total of 313 pediatric cases of IEI, 71% diagnosed at molecular level, were registered with a cumulative follow-up period of 29,734 months. Skin manifestations were seen in 40.3% of the patients, and they were among the presenting manifestations in 33%. Patients with skin manifestations were older at both onset and diagnosis ages of IEI symptoms, but this was statistically significant for the latter only. The diagnosis delay was significantly longer in patients with skin manifestations. There was a statistically significant association between having skin manifestations and IEI category, being more common in patients with complement deficiencies, combined immunodeficiencies, and diseases of immune dysregulation. There was no statistically significant association between having skin manifestations and both gender and survival. Skin infections were the most frequent manifestations followed by eczema and autoimmune associations. Among IEI with more than 10 cases, skin lesions were a consistent finding in dedicator of cytokinesis 8 (DOCK8) deficiency, hyper IgE syndrome, ataxia-telangiectasia, and recombination activation gene (RAG)1 deficiency.
Conclusions: Skin manifestations are common in IEI patients, and they had significant diagnosis delay and referral to specialists. Improvement of awareness about IEI is needed among pediatricians and dermatologists.
RESULTS: Twenty-two patients (from 16 unrelated families) were molecularly diagnosed as XLA. Genetic testing revealed fifteen distinct mutations, including four splicing mutations, four missense mutations, three nonsense mutations, three short deletions, and one large indel mutation. These mutations scattered throughout the BTK gene and mostly affected the kinase domain. All mutations including five novel mutations were predicted to be pathogenic or deleterious by in silico prediction tools. Genetic testing confirmed that eleven mothers and seven sisters were carriers for the disease, while three mutations were de novo. Flow cytometric analysis showed that thirteen patients had minimal BTK expression (0-15%) while eight patients had reduced BTK expression (16-64%). One patient was not tested for monocyte BTK expression due to insufficient sample. Pneumonia (n=13) was the most common manifestation, while Pseudomonas aeruginosa was the most frequently isolated pathogen from the patients (n=4). Mild or asymptomatic COVID-19 was reported in four patients.
CONCLUSION: This report provides the first overview of demographic, clinical, immunological and genetic data of XLA in Malaysia. The combination of flow cytometric assessment and BTK genetic analysis provides a definitive diagnosis for XLA patients, especially with atypical clinical presentation. In addition, it may also allow carrier detection and assist in genetic counselling and prenatal diagnosis.