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.

The malnutrition screening tool STRONGKIDS performed better than other screening tools for children hospitalised in Egypt.

AIM: To compare the accuracy of three different screening tools, namely, the Paediatric Yorkhill Malnutrition Score (PYMS), Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP), and Screening Tool for Risk on Nutritional Status and Growth (STRONGKIDS), in assessing malnutrition risk in hospitalised children. METHODS: A cross-sectional study was conducted on 300 children aged 6 months to 15 years at Alexandria University Children's Hospital, Egypt. The sensitivity and specificity of each tool were calculated to detect acute and chronic malnutrition, and an agreement test was conducted between the nutritional screening tools. The patients were classified into different nutritional risk groups, and their classification was compared with anthropometric measures and clinical variables, such as the length of hospital stay (LOS). RESULTS: The prevalence of stunting and wasting on admission was found to be 3% and 6.6%, respectively. Children categorised as high-risk on admission had a longer LOS than those at low risk. The agreement test between the STAMP score and STRONGKIDS score on admission showed the most significant agreement, and STRONGKIDS had the best accuracy in detecting acute and chronic malnutrition. CONCLUSION: The comparison of the three screening tools revealed that STRONGKIDS exhibited the best accuracy in detecting acute and chronic malnutrition.

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.

Clinically Relevant KCNQ1 Variants Causing KCNQ1-KCNE2 Gain-of-Function Affect the Ca2+ Sensitivity of the Channel.

Dominant KCNQ1 variants are well-known for underlying cardiac arrhythmia syndromes. The two heterozygous KCNQ1 missense variants, R116L and P369L, cause an allelic disorder characterized by pituitary hormone deficiency and maternally inherited gingival fibromatosis. Increased K+ conductance upon co-expression of KCNQ1 mutant channels with the beta subunit KCNE2 is suggested to underlie the phenotype; however, the reason for KCNQ1-KCNE2 (Q1E2) channel gain-of-function is unknown. We aimed to discover the genetic defect in a single individual and three family members with gingival overgrowth and identified the KCNQ1 variants P369L and V185M, respectively. Patch-clamp experiments demonstrated increased constitutive K+ conductance of V185M-Q1E2 channels, confirming the pathogenicity of the novel variant. To gain insight into the pathomechanism, we examined all three disease-causing KCNQ1 mutants. Manipulation of the intracellular Ca2+ concentration prior to and during whole-cell recordings identified an impaired Ca2+ sensitivity of the mutant KCNQ1 channels. With low Ca2+, wild-type KCNQ1 currents were efficiently reduced and exhibited a pre-pulse-dependent cross-over of current traces and a high-voltage-activated component. These features were absent in mutant KCNQ1 channels and in wild-type channels co-expressed with calmodulin and exposed to high intracellular Ca2+. Moreover, co-expression of calmodulin with wild-type Q1E2 channels and loading the cells with high Ca2+ drastically increased Q1E2 current amplitudes, suggesting that KCNE2 normally limits the resting Q1E2 conductance by an increased demand for calcified calmodulin to achieve effective channel opening. Our data link impaired Ca2+ sensitivity of the KCNQ1 mutants R116L, V185M and P369L to Q1E2 gain-of-function that is associated with a particular KCNQ1 channelopathy.

Effect of early feeding practices and eating behaviors on body composition in primary school children.

BACKGROUND: Understanding children's feeding practices and eating behaviors is important to determine etiology of childhood obesity. This study aimed to explore the relationship between early feeding practices, eating behavior and body composition among primary school children. METHODS: The data were collected from 403 primary school children. They were administered structured questionnaire, including sociodemographic characteristics, early feeding practices and Child's Eating Behavior Questionnaire. Anthropometric and blood pressure (BP) measurements were performed. RESULTS: Children with obesity and overweight showed higher food approach subscales and lower food avoidance subscales compared to a healthy and underweight child. Children who were exclusively or predominantly breast fed during the first 6 months had the lowest scores for the food approach subscales, food responsiveness (FR) and emotional overeating (EOE) and had the highest scores for the food avoidance subscales, satiety responsiveness (SR) and emotional under eating (EUE). Children who were introduced solid food after 6 months showed lower scores for FR, enjoyment of food and EOE but scored highest for SR, slowness in eating (SE) and EUE. All anthropometric measurements were positively correlated with all food approach subscales and negatively with SE, SR and food fussiness. All food approach subscales were positively correlated with BP percentiles. All food avoidance subscales were negatively correlated with both BP percentiles, except for EUE, which was negatively correlated with diastolic BP percentile only. Age, SR, SE and FR were predictors for child body mass index. CONCLUSION: Early feeding practices and eating behavior are considered as prevention approaches for obesity.

Sensory Processing and Gastrointestinal Manifestations in Autism Spectrum Disorders: No Relation to Clostridium difficile.

The role of the gut microbiota in triggering autism is a rapidly emerging field of research. Gut microbiota have been incriminated because autistic children often have gastrointestinal symptoms. Pathogenic gut bacteria in children with autism spectrum disorders (ASD) have been reported. The present study aimed to assess Clostridium difficile in the stool of children with ASD and its relation to gastrointestinal (GI) comorbidities, autism severity, and sensory impairment. The study included 58 ASD patients, 45 of their neurotypical siblings, and 45 unrelated controls. Childhood Autism Rating Scale (CARS) was used to assess the severity of autism. Sensory problems were evaluated using the Short Sensory Profile (SSP). GI symptoms were assessed with a modified six-item GI Severity Index (6-GSI) questionnaire. Quantitative real-time PCR was done for the detection and quantitation of C. difficile and its toxins A and B. C. difficile was detected in 25.9%, 40%, and 15.6% of ASD cases, siblings, and unrelated control respectively. Regarding toxin A and B production, 73.3%, 77.8%, and 71.4% of C. difficile in positive ASD, siblings, and unrelated control cases respectively were toxigenic. There was no statistically significant difference between the three groups as regards C. difficile qualitative, quantitative, and toxin production results. In conclusion, C. difficile is not specifically prevalent in the gut of children with ASD. Although most of the strains are toxigenic, there were no GI symptoms in the control groups and no statistically significant association with GI Severity Index in autistic cases. Gastrointestinal dysfunction and sensory impairment are common comorbidities in ASD.

Bovine Colostrum in the Treatment of Acute Diarrhea in Children: A Double-Blinded Randomized Controlled Trial.

OBJECTIVES: To evaluate the effect of bovine colostrum (BC) on the treatment of children with acute diarrhea attending the outpatient clinic. METHODS: This double-blind randomized controlled trial was conducted on 160 children with diarrhea; 80 cases were randomly treated with BC group and 80 cases randomly received placebo (placebo group). All cases were investigated for bacterial causes of diarrhea (Salmonella spp, Shigella spp, diarrheagenic E. coli (DEC), Campylobacter spp., and Vibrio cholerae) as well as for Rotavirus antigen in stool. RESULTS: After 48 h, the BC group had a significantly lower frequency of vomiting, diarrhea and Vesikari scoring compared with the placebo group (p = 0.000, p = 0.000, p = 0.000, respectively), whether it was due to Rotavirus or E. coli infection. CONCLUSIONS: BC is effective in the treatment of acute diarrhea and can be considered as adjuvant therapy in both viral and bacterial diarrhea to prevent diarrhea-related complications.