Background
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathological immune activation characterized by clinical signs and symptoms of extreme inflammation. It results from the uninhibited proliferation and activation of cells of the macrophage lineage and leads to the production of excess amounts of pro-inflammatory cytokines. The familial form of HLH disease is due to mutations in several genes necessary for natural killer (NK) cell and T cell granule-mediated cytotoxic function. These genes are involved in sorting, trafficking, docking, and fusion of cytotoxic granules containing granzymes A and B and perforin to the cell membrane of the target cell (using the proteins LYST, AP-3 complex, Rab27a, Munc 13–4, Munc 18–2, syntaxin 11). Defect in any of those proteins results in defective cytotoxicity. Consequently, genes included in these steps play valuable roles in the pathogenesis of familial HLH disease including perforin (PRF1) gene in which defect causes familial HLH type 2 (FHL2).
Case presentation
A 2-year-old boy suffered from hepatosplenomegaly and fever. He fulfilled the required criteria for the diagnosis of HLH according to HLH-2004 diagnostic criteria. We screened the patient for the presence of mutations in the coding exons and of PRF1 gene by PCR amplification of genomic DNA followed by direct sequencing of the PCR products. We report a novel homozygous deletion/insertion frameshift mutation in PRF1 gene (M28393: exon 2: c.536delAinsCG p.F178fs). We treated him with HLH 2004 protocol of treatment and showed a remarkable response with resolution of fever and decrement in the size of hepatosplenomegaly.
Conclusions
Our study discovered a novel frameshift mutation in PRF1 gene in an infant with HLH disease, and it is the first report of this type of mutation in Egyptian patients with this disease.
The recognition and diagnosis of primary immunodeficiency disorders (PIDs) is challenging in developing countries. This study aimed to describe the features of PID patients in a tertiary care setting in Egypt and analyse the distribution, clinical features and outcome of PID among paediatric patients. Methods: This cross-sectional retrospective study was conducted between January 2016 and January 2021, to evaluate all paediatric patients aged below 18 years with PID that were diagnosed according to the International Union of Immunological Societies 2017 classification. We retrospectively studied the clinical features, diagnostic spectrum, laboratory investigations and relevant immunological workup, and treatment options. Results: A total of 61 PID patients were enrolled in the current study. The median age at diagnosis was 22 months. The overall consanguinity rate was 49.2%, and the family history of PID was 19.7%. Among all PIDs, the combined immunodeficiency with syndromic features predominates with 17 cases, accounting for 27.9% of all cases of PIDs. The predominant antibody deficiency was the second common PID that was diagnosed in 14 patients (23%). Recurrent pneumonia was the most common initial presentation, occurring in 77% of patients, followed by failure to thrive (63.9%), and recurrent otitis media (55.7%). The total deaths were 18 patients (29.5%). Conclusion: Paediatric patients with PIDs are not uncommon in Egypt. There is a need to improve PID diagnosis and treatment, for better estimation of PID and to decrease morbidity and mortality.
Aim: We aimed to evaluate MIS-C patients' clinical manifestations, laboratory test results and mortality outcomes in an Egyptian tertiary care university hospital. Methods: We conducted a 12 month cross-sectional study in a tertiary-care university children's hospital. All paediatric patients (1 month to 16 years old) who met the CDC criteria for MIS-C were enrolled in the study. We assessed patients' clinical presentations, complications, treatments, imaging studies, laboratory test results and outcomes. The baseline clinical and laboratory findings of survivors and non-survivors were compared. Results: Of 45 MIS-C patients, 24 (53.3%) were males, and the median (interquartile range) age was 4 (1.25-10) years. All patients had fever, 64.4% had respiratory manifestations, 48.9% presented with coma, 44.4% presented with shock, 33.3% presented with seizures, 31.1% had abdominal pain, 28.9% had vomiting and 22.2% presented with cerebrovascular stroke. A total of 15 (33.3%) patients died, and the non-survivors had a significantly higher incidence of respiratory manifestations (P = 0.028), shock (P = 0.034), cerebrovascular stroke (P = 0.043) and seizures (P = 0.044) as compared to the survivors. In addition, the serum levels of ferritin (P = 0.047), alanine aminotransferase (P = 0.047) and aspartate aminotransferase (P = 0.05) were significantly higher in the non-survivors as compared to the survivors. Conclusions: Based on our findings, MIS-C associated with COVID-19 is a potentially fatal illness. Hospitalised patients with MIS-C often have multi-organ injuries affecting the respiratory, cardiovascular, gastrointestinal and neurological systems. The deceased are more likely to exhibit respiratory manifestations, shock, cerebrovascular stroke, seizures and elevated serum levels of ferritin and liver enzymes.
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