A Rare Case of Neonatal Hypomagnesemia with Secondary Hypocalcemia Caused by a Novel Homozygous TRPM6 Gene Variant.

BACKGROUND Familial hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disorder (OMIM# 602014) caused by mutations in the gene encoding transient receptor potential melastatin 6 (TRPM6)) on chromosome 9q22, a channel involved in epithelial magnesium resorption. While a plethora of studies have delineated various clinical manifestations pertinent to this mutation, the literature is devoid of connections between TRPM6 mutations and bleeding diathesis, or sudden infant death syndrome (SIDS). This report presents a case of familial HSH associated with the novel homozygous TRPM6 gene variant c.5281C>G p. (Arg1761Gly) chr9: 77354845. CASE REPORT This report details a 26-day-old neonate, born full term with optimal Apgar scores, who experienced an abrupt emergence of apnea, cyanosis, bilateral nasal bleeding, and diminished alertness. Despite the neonate's initially unremarkable clinical birth indicators, a meticulous assessment unveiled a pronounced family history of SIDS, including a sibling previously diagnosed with hypomagnesemia. Laboratory examination of the infant demonstrated severe hypomagnesemia and hypocalcemia, conditions which were promptly ameliorated following intravenous administration of magnesium and calcium. Whole-exome sequencing identified a homozygous TRPM6 gene mutation c.5281C>G p. (Arg1761Gly) at chr9: 77354845. This gene is crucial for magnesium regulation. The mutation involves a cytosine-to-guanine shift, resulting in an arginine to glycine amino acid substitution at position 1761 of the TRPM6 protein. CONCLUSIONS This report has highlighted that infantile hypomagnesemia may be associated with symptoms and signs that can mimic infection, or it can present with seizures. Although familial HSH is a rare genetic disorder that can be identified by genetic testing, correction of hypomagnesemia is the most important and immediate clinical management strategy.

Impact of Respiratory Viruses and SARS-CoV-2 on Febrile Seizures in Saudi Children: Insights into Etiologies, Gender, and Familial Associations.

BACKGROUND Childhood febrile seizures occur between 5 months and 6 years of age in children without a previous history of seizure and are associated with high temperature in the absence of intracranial infection. This retrospective study identified 71 children aged 6 months to 5 years with febrile seizures between 2017 and 2021 at a single center in Saudi Arabia and aimed to identify an association between common respiratory virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MATERIAL AND METHODS Pediatric nasopharyngeal specimens were tested using a multiplex PCR respiratory panel detecting human coronaviruses (NL63, 229E, OC43, HKU1), influenza A/B, human adenovirus, parainfluenza viruses 1-4, respiratory syncytial virus, human metapneumovirus, rhinovirus/enterovirus, Middle East respiratory syndrome coronavirus, and, as of September 2021, SARS-CoV-2, confirmed using the Cepheid Xpert Xpress SARS-CoV2 RT-PCR kit. RESULTS In a cohort of 71 pediatric patients (median age, 19 months; 54.9% female), dominant pathogens included human rhinovirus/enterovirus (23.9%), influenza A/B (26.8%), and SARS-CoV-2 (14.1%). Concurrent infections were noted in 28.2%. Simple seizures occurred in 69%, and complex seizures in 31%. Females exhibited an 8.18-fold increased risk for complex seizures. Each additional fever day reduced complex seizure risk by 36%. Familial seizure history increased risk 8.76-fold. Human rhinovirus/enterovirus or parainfluenza infections inversely affected complex seizure likelihood compared with adenovirus. CONCLUSIONS In Saudi children with febrile seizures, distinct viral etiologies, sex, and familial links play pivotal roles. Given regional viral variations, region-tailored diagnostic and therapeutic strategies are paramount. A multicenter prospective cohort study is essential for comprehensive understanding.

Pathogenic Novel Heterozygous Variant c.1076c>T p. (Ser359Phe) chr1: 120512166 in NOTCH2 Gene, Type 2 Alagille Syndrome Causing Neonatal Cholestasis: A Case Report.

BACKGROUND Alagille syndrome (ALGS) is a multisystem hereditary illness with a dominant pattern and partial penetrance. Multiple organ abnormalities can be caused by mutations in the Jagged canonical Notch ligand 1 (JAG1) gene. Notch receptor 2 (NOTCH2) gene mutations are also uncommon. ALGS is also characterized by deformed or narrowed bile ducts and is notoriously difficult to diagnose due to the wide range of symptoms and absence of unambiguous genotype-phenotype connections. Little is known about ALGS patients who have NOTCH2 mutations. We present a patient who developed progressive liver failure due to a unique pathogenic heterozygous variation of the NOTCH2 gene, c.1076c>T p. (Ser359Phe) chr1: 120512166, resulting in type 2 ALGS. CASE REPORT A Saudi Arabian newborn with bilateral hazy eyes, ectropion, dry ichthyic skin, normal male genitalia, and bilateral undescended testes was born at 31 weeks. Previous miscarriages, pregnancy-induced maternal cholestasis, fatty liver, or neonatal jaundice were not reported in the family history. He had developed worsening cholestatic jaundice by the third week of hospitalization. The extensive work-up for metabolic, infectious, and other relevant etiologies was negative. Following gram-negative sepsis, he died of multiorgan failure. A NOTCH2 gene mutation explained the phenotypic difference in our situation. Another intriguing observation was the presence of ichthysis and craniosynostosis in ALGS with a NOTCH2 mutation. CONCLUSIONS Cholestasis in newborns can be difficult to diagnose. Next-generation sequencing detects 112 copy number variants in the cholestasis gene panel blood test. More research is needed to understand why NOTCH2 mutations are relatively rare in ALGS.

Can inverse probability treatment weighting (IPTW) be used to assess differences of CRBSI rates between non-tunneled femoral and jugular CVCs in PICU patients?

BACKGROUND: In children in the ICU, catheter-related bloodstream infections (CRBSI) have also been linked to mortality, morbidity, and healthcare costs. Although CRBSI poses many potential risks, including the need to avoid femoral access, there is debate regarding whether jugular access is preferable to femoral access in adults. Study reports support both perspectives. There is no consensus in meta-analyses. Children have yet to be examined in depth. Based on compliance with the central line bundle check lists, we aim to determine CRBSI risk in pediatric intensive care units for patients with non-tunneled femoral and internal jugular venous access. METHODS: A retrospective cohort study was conducted on patients with central venous catheters in the pediatric ICU of King Abdulaziz University Hospital between January 1st, 2017 and January 30th, 2018. For the post-match balance, we use a standardized mean difference of less than 0.1 after inverse probability treatment weighting for all baseline covariates, and then we draw causal conclusions. As a final step, the Rosenbaum sensitivity test was applied to see if any bias influenced the results. RESULTS: We recorded 145 central lines and 1463 central line days with 49 femoral accesses (33.79%) and 96 internal jugular accesses (66.21%). CRBSI per 1000 central line days are 4.10, along with standardized infections of 3.16. CRBSI risk differed between non-tunneled femoral vein access and internal jugular vein access by 0.074 (- 0.021, 0.167), P-value 0.06, and relative risk was 4.67 (0.87-25.05). Using our model, the actual probability was 4.14% (0.01-0.074) and the counterfactual probability was 2.79% (- 0.006, 0.062). An unobserved confounding factor was not identified in the sensitivity analysis. CONCLUSIONS: So long as the central line bundle is maintained, a femoral line does not increase the risk of CRBSI. Causation can be determined through propensity score weighting, as this is a trustworthy method of estimating causality. There is no better way to gain further insight in this regard than through the use of randomized, double-blinded, multicenter studies.

Patterns and Determinants of Change in Cortisol Levels and Thyroid Function as a Function of Cardiac Risk in Children Undergoing Cardiac Surgery.

BACKGROUND: Children undergoing cardiac surgery with cardiopulmonary bypass (CPB) are exposed to the risk of hormonal imbalances resulting from acute stress, which may eventually result in high postoperative mortality and morbidity. OBJECTIVE: We assessed adrenal and thyroid hormonal changes and their determinants following cardiac surgery in children and explored their prognostic value in predicting cardiac outcomes. Study Design and Methods. A prospective cohort study was conducted at King Abdulaziz University Hospital (KAUH), between 2017 and 2018. The study involved 46 children aged 14 years or younger who underwent elective cardiac surgery with cardiopulmonary bypass. Serum levels of cortisol, TSH, fT3, and fT4 were measured preoperatively and 24, 48, and 72 hours after surgery. The cardiac risk was assessed using the risk adjustment for congenital heart surgery (RACHS) scale. A composite cardiovascular outcome was analyzed as a numerical variable and calculated as the number of cardiovascular events. RESULTS: Overall, the changes in thyroid function parameters resulted in a U-shaped curve, while cortisol levels yielded a bell-shaped curve. The most significant changes occurred at 24 hours postop, including a decrease in mean TSH by 2.08 µIU/L (p < 0.001), fT3 by 2.39 pmol/L (p < 0.001), and fT4 by 2.45 pmol/L (p < 0.001) and an increase in cortisol levels by 406.48 nmol/L (p < 0.001) with respect to the baseline. Cortisol concentration peaked higher and recovered slower among patients with high cardiac risk than their counterparts. Cardiovascular outcomes were independently predicted by the extent of the decline in fT4 and TSH at 48 and 72 hours postop, with reference to the baseline, and by the cortisol level at 24 h postop, independent of the baseline, besides the RACHS category. CONCLUSION: Cardiac surgery among children yields a high adrenocortical response and a high incidence of nonthyroidal illness syndrome, increasing cardiovascular risk. A preventive management strategy involves improving surgical techniques to minimize trauma-related stress.

An 11-Year-Old Saudi Arabian Girl Who Presented with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 Infection with Coronary Artery Aneurysm and Cardiac Involvement: A Case Report.

BACKGROUND Early in the COVID-19 pandemic, children who were infected with severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) with vascular inflammation were described as having a vasculitis similar to Kawasaki's disease. There are now consensus clinical guidelines that have described the presentation and diagnosis of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection. This report aims to describe a case of MIS-C in an 11-year-old Saudi Arabian girl who presented with coronary artery aneurysm and cardiac involvement. CASE REPORT We describe an 11-year-old Saudi girl who was asymptomatic for 3 weeks after contracting SARS-CoV-2. Three weeks after suffering a mild flulike illness, she developed a high fever, cough, and severe clinical deterioration within 12 h of admission, including shock, rash, pleural effusion, high inflammatory markers, and a coronary aneurysm. As per current practice, the diagnosis was confirmed as multisystem inflammatory syndrome based on a SARS-CoV-2 test with reverse transcription polymerase chain reaction (RT-PCR) from 2 nasopharyngeal aspirates. Her condition was successfully treated with antibiotics, inotropes, IVIG, aspirin, and Tocilizumab, in addition to high-flow oxygen therapy. Eventually, she was able to return home after fully recovering. CONCLUSIONS The findings in this report suggest that children with MIS-C due to SARS-CoV-2 infection can have a good prognosis, even when they suffer from coronary artery and cardiac involvement. The increasing number of emerging SARS-CoV-2 variants that affect children supports the importance of RT-PCR for the COVID-19 diagnostic test for children with multisystem or cardiovascular inflammation, which may guide the most appropriate clinical management of the variants of MIS-C.