A case report of an Egyptian family with familial hypercholesterolemia and an exonic LINE-1 insertion in LDLR.

BACKGROUND: Familial hypercholesterolemia (MIM: PS143890) is a genetic disorder characterized by an increase in blood cholesterol. LDLR is one of the genes which their defect contributes to the disorder. Affected individuals may carry a heterozygous variant or homozygous/compound heterozygous variants and those with biallelic pathogenic variants present more severe symptoms. METHOD: We report an Egyptian family with familial hypercholesterolemia. Both the proband and parents have the disorder while a sibling is unaffected. Exome sequencing was performed to identify the causal variant. RESULTS: LINE-1 insertion in exon 7 of LDLR was identified. Both parents have a heterozygous variant while the proband has a homozygous variant. The unaffected sibling did not carry the variant. DISCUSSION: This insertion may contribute to the high prevalence of hypercholesterolemia in Egypt and the finding underscores the importance of implementing mobile element insertion caller in routine bioinformatics pipeline.

Evaluation of non-thyroidal illness syndrome in shock patients admitted to pediatric intensive care unit in a developing country.

During critical illness, children my experience various changes in their thyroid hormone levels. Such changes are termed non-thyroidal illness syndrome (NTI). The extent of change correlates with the severity of the illness and its outcomes in critically ill patients. This study aimed to investigate the correlation between the severity of shock and thyroid hormone derangement. This prospective observational study included forty patients aged one month to five years who were admitted to the pediatric intensive care unit (PICU) with shock. Thyroid function tests were conducted on admission, after shock reversal, and five days later. NTI patterns were observed in 70% of patients. The PIM2 score showed a significant negative correlation with T3 (r = - 0.353, p = 0.026) and FT3 levels on admission (r = - 0.417, p = 0.007). Furthermore, after shock reversal, the PIM2 score continued to exhibit significant negative correlations with T4 (r = - 0.444, p = 0.004), T3 (r = - 0.329, p = 0.038), FT3 (r = - 0.355, p = 0.025), and FT4 levels (r = - 0.379, p = 0.016).    Conclusion: This study underscores the high prevalence of NTI in PICU shock patients and suggests monitoring thyroid hormone levels for outcome prediction and treatment guidance. Further research is needed to optimize NTI management in critically ill children. What is Known: • Non-thyroidal illness syndrome (NTIS) is a condition observed in critically ill patients. • There has been limited research on NTI in children, and existing studies have generated conflicting results regarding the relationship between thyroid hormones and clinical outcomes in cases of sepsis and septic shock. What is New: • The study has revealed dynamic changes in free triiodothyronine (FT3) levels during the process of shock reversal and recovery in children who experienced shock. • A significant negative correlation was found between the Pediatric Index of Mortality 2 (PIM2) score and several thyroid hormone levels, including FT3 on admission and T4, FT3, and FT4 on shock reversal.

Cyclin D2 gene variance and expression level in pediatric acute lymphoblastic leukemia.

BACKGROUND: Cyclin D2 (CCND2) is a crucial player in cell cycle regulation. CCND2 polymorphisms contribute to cancer predisposition. OBJECTIVES: To evaluate the association of CCND2 rs3217927 single nucleotide polymorphisms (SNP) and its expression levels with acute lymphoblastic leukemia (ALL) susceptibility in Egyptian children and its potential prognostic role. METHODS: The 5' nuclease allelic discrimination assay was used to evaluate the frequency of CCND2 rs3217927 SNP in 80 newly diagnosed children with ALL and 80 age- and sex-matched controls. CCND2 relative expression levels were determined by real-time quantitative polymerase chain reaction. RESULTS: The genotype analysis revealed that the GG genotype and G allele were significantly more prevalent among ALL patients than controls (p Ë‚ .001). Regression analysis demonstrated that Egyptian children carrying only one G allele had about 31-fold increased risk to develop ALL compared to A allele carriers. CCND2 was overexpressed in ALL patients compared to controls (p < .001). The CCND2 overexpression was associated with the GG genotype and G allele (p < .001). Furthermore, G allele was an independent negative prognostic marker for central nervous system (CNS) involvement (odds ratio [OR] = 4.676; 95% confidence interval [CI]: 1.2-18.6), risk stratification (OR = 38; 95% CI: 7.7-188.2), and chemoresistance (OR = 9.864; 95% CI: 5.6-70.3) in ALL patients. CONCLUSIONS: G allele of CCND2 rs3217927 SNP might be associated with increased risk for ALL in Egyptian children besides being an independent negative prognostic marker for their risk stratification and therapeutic outcome. CCND2 rs3217927 SNP genotyping might be used to demarcate ALL patients with aggressive disease phenotypes who may be candidate for alternative targeted therapeutic strategies.

Faecal calprotectin in COVID-19 patients with intestinal symptoms.

Introduction: Extra-pulmonary manifestations of the Coronavirus disease of 2019 (COVID-19) have been increasingly reported, especially gastrointestinal and hepatic system dysfunction. The concern of faecal-oral transmission for COVID-19 was raised. Aim: To study the trend of faecal calprotectin in COVID-19 patients with intestinal symptoms. Material and methods: Forty confirmed cases of COVID-19 infection presenting with diarrhoea were subjected to a thorough history taking, clinical examination, and routine laboratory investigations. They were treated according to the Egyptian MOH guidelines. Faecal calprotectin (FC) concentration was measured at initial presentation and after 3 months. Those who had persistently elevated levels ≥ 200 µg/g were subjected to colonoscopic examination and histopathological examination. Forty confirmed cases of COVID-19 without diarrhoea were recruited as a control group in the initial FC evaluation. Results: Faecal calprotectin was found to be significantly elevated in the studied COVID-19 patients who presented with diarrhoea, with a mean value 260 ±80 µg/g compared to the those without diarrhoea, with a mean value of 31.6 ±12.9 µg/g (p < 0.001). Moreover, 20% (8 patients) had an elevated level exceeding 200 µg/g 3 months after recovery; among them, 5 patients showed mild colonoscopic changes whereas 3 patients showed severe ileocolitis. Out of the 3 patients with marked ileocolitis, 2 showed histopathological changes raising the diagnosis of Crohn's disease. Conclusions: Faecal calprotectin was found to be elevated in COVID-19 patients with intestinal symptoms, especially diarrhoea, with or without colonoscopic and histopathological changes.