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Background: Familial hemophagocytic lymphohistiocytosis (HLH) results in clinical manifestations of an extreme inflammatory process; leading to an overlap with other diseases with a hyperinflammation process. Implementing HLH criteria without genetic analysis might lead to inadvertent planned therapy with immunosuppressive and unnecessary bone marrow transplantation. Objectives: This study assessed the frequency and types of UNCD mutations among patients clinically diagnosed with Familial HLH or systemic inflammatory response syndrome and correlated between the genetic mutations and clinical picture. Methods: This study included 40 patients who were clinically diagnosed as Familial HLH or systemic inflammatory response syndrome with median age 28 months. All patients fulfilled at least 5 out of 8 of HLH criteria. Complete blood count, liver enzymes, total and direct bilirubin, serum ferritin, serum fibrinogen, serum triglycerides, sCD25, bone marrow aspirate, MRI brain and CSF analysis were assessed as well as analysis of UNC13D gene were performed. Results: The studied population included 24 (60%) males and 16 (40%) females with median age at initial presentation being 26 months. Eighteen (45%) patients had a positive family history. At presentation, 25 (62.5%) patients had systemic manifestations: 36 (90%) patients had fever, 35 (87.5%) patients had hepatosplenomegaly. Nine (22.5%) patients presented with neurological manifestations and six (15%) patients had both systemic and neurological manifestations. Genetic testing of the studied population showed: 10 (25%) patients had UNCD gene mutation, 15 (37.5%) patients were found to have other gene mutations for FHLH, 3 patients had mutations for other genetic conditions while 12 (40%) patients had no any genetic mutations. Among the 15 patients who showed gene mutations for other FHLH subtypes; 12 (40%) patients had Perforin gene mutations, 1 patient had STXBP2 gene mutation, 1 patient had Lyst gene mutation and 1 patient had RAB27A gene mutations. Data showed no significant difference in clinical presentation between patients with UNCD gene mutation and other patients (Pvalue: 0.08). Nearly one third of patients (n = 11, 30.6%) were misdiagnosed and treated as FHLH which was then excluded by genetic study. 8 (32%) patients were diagnosed solely by genetic study to have FHLH and were not suspected upon presentation to have FHLH with a mean interval to diagnosis of 203 days. Conclusions: Genetic testing is mandatory for diagnosis of FHLH to determine the exact gene mutation and to differentiate from other conditions with hyperinflammatory process to rapidly implement bone marrow transplantation in patients with positive mutations as it is the only radical cure. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a major health concern and is predicted to become the leading cause of end-stage liver disease in the coming decades. Few studies examined the frequency of NAFLD in childhood acute lymphoblastic leukemia (ALL). Aim: To assess the prevalence of NAFLD in children with ALL at various phases of treatment. The study also investigates the impact of different treatment regimens and other risk factors on NAFLD development in this population. Methods: This cross-sectional study with prospective follow up for the newly diagnosed group of patients included 60 children with ALL recruited from the Pediatric Oncology Unit at Ain Shams University Children's Hospital. We collected data including sociodemographic data, age at diagnosis of ALL, diagnosis and risk stratification, treatment regimens, as well as 24-hour dietary recall. All patients were assessed for anthropometric measurements, body composition analysis, abdominal examination, laboratory investigations including liver function tests and lipid profile in addition to abdominal ultrasound. Results: The mean age of the studied patients was 8.9 years. Among all studied groups, 56% of the post-induction group, 10% of patients during the maintenance phase and 25% post-completion of therapy had NAFLD. Regarding protocol of therapy in all patients who received chemotherapy, (100%) of patients who had received total XV-HR as a protocol of therapy had NAFLD with p-value = 0.023, on the other hand there was no difference found between patients with and without NAFLDregarding total XV-LR and total XV-SR protocols with p value 0.436 and 0.933 respectively. Among all studied groups, patients with NAFLD had higher median energy level (3272 kcal/d in NAFLD vs 1834 kcal/d in non-NAFLD, p = 0.021), higher median fat intake (87 g/d for NAFLD vs 49 g/d for non-NAFLD, p = 0.046), higher median carbohydrate intake (486 g/d for NAFLD vs 274 g/d for non NAFLD, p = 0.016) and higher median fructose containing beverages (2 per month for NAFLD group versus 0 per month for non-NAFLD group p = 0.041). Additionally, NAFLD group showed higher median triceps skin fold thickness z-score of 0.09 vs -0.51 in non-NAFLD group, p = 0.002. However, there was no difference between patients with and without NAFLD in all studied patients regarding body composition parameters. Higher percentage (42.9%) of patients who had high LDL level (mg/dl) had been found in NAFLD group versus (10.9%) in non NAFLD, p = 0.022, while there was no difference found between patients with and without NAFLD in all studied patients regarding LDL serum levels. Body fat percentage positively correlated with serum LDL-cholesterol during ALL treatment with (r = 0.508, and p = 0.044). There was no difference found between patients with and without NAFLD in all treatment phases regarding median ALT (21, 18 IU/L in non-NAFLD and NAFLD group respectively), p = 0.588, median AST serum level (28, 30 IU/L in non-NAFLD and NAFLD group respectively), p = 0.612. Conclusion: NAFLD is a relatively common finding in childhood ALL especially in the post-induction phase. ALL patients treated with total XV-HR protocol of therapy more frequently developed NAFLD than patients on total XV-LR and total XV-SR protocols. NAFLD patients had significantly higher dietary intake compared to non NAFLD patients. There was a positive correlation between body fat percentage and serum levels of LDL in children during ALL treatment. [ABSTRACT FROM AUTHOR]