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  Detection of Chromosomal Mosaicism- the Importance of Karyotyping and FISH

  Allison Kalinousky, Jennifer Roberts, Madeeha Alikhan, John Herriges, Lei Zhang, and Elena Repnikova

  Introduction: The use of whole-exome/whole-genome sequencing for the detection of sequence-level variants and copy number variations (CNV) is increasingly being adopted as a primary testing method for genetic disease diagnosis by many institutions. Additionally, long-read sequencing is a promising technique to capture not only sequence level variants and CNVs but also structural chromosomal abnormalities. Significant progress has been achieved in this field; however, the detection of chromosomal mosaicism, including numerical gains and losses, rings, markers, and structural rearrangements – particularly those that are lineage-specific or exist at low levels – might still pose challenges with these emerging technologies. Furthermore, differentiating various mosaic cell lines may not be feasible. Literature review shows that chromosomal mosaicism is estimated to occur in up to 70% of human preimplantation embryos. Clinically significant chromosomal mosaicism is reported in ~3% of products of conceptions (POC), 1-2% of chorionic villus sampling (CVS), 0.1-0.3% of amniotic fluids (AF) samples, and 0.05-0.1% postnatal samples when assessed using conventional cytogenetic methods. To date, there are no studies available that provide data on the accuracy and detection levels of chromosomal mosaicism using third of fourth generation sequencing technologies. Methods: We conducted a retrospective review of patients who underwent conventional cytogenetic testing (chromosome analysis via Giemsa staining and fluorescence in situ hybridization (FISH)) for various clinical indications at Children’s Mercy Hospital from 2003 and 2023. Within this period, we received 20,866 constitutional cases of with 4,414 were cytogenetically abnormal. We also evaluated 762 cases submitted for exome sequencing with copy number analysis in 2023. We then examined all mosaic cases. Results: We found that the average number of mosaic cases each year was 29 (range: 9-39), accounting for ~3.1% of all clinical cases studied and ~14% of all abnormal cases per year. Levels of mosaicism were variable, ranging from 4 to 95%. Of all cases (both normal and abnormal) across all years, 4.7% of POCs, 4.3% of AF samples, and 2.7% of peripheral blood (PB) samples had chromosomal mosaicism. In comparison to the 762 PB exome cases, only three were mosaic (two with trisomy 9 and a ring(X)) totaling ~0.4% of postnatal cases. Numerical abnormalities are the most common form of mosaicism in our cohort, accounting for ~79% of mosaic cases. Of the numerical abnormalities, sex chromosomes are the most frequently implicated, with an average involvement of 44% in POCs, 40% in AF samples, and 79% in PB. The most common numerical abnormality of the autosomes in POCs were affecting chromosomes 22 (7%), 15 (6%), and 16 (5%); in AF samples affecting chromosomes 21 (20%), 18 (7.5%), and 22 (5%); and in PBs affecting chromosomes 21 (11%) and 18 (4%). Approximately 14% of mosaic cases harbored a structural abnormality of the autosomes. The most common abnormality in PBs involved the Y chromosome (12%), and in POCs involved chromosome 13 (19%). The structural abnormalities in AF samples affected chromosomes 3, 7, 9, 12, 14, 16, 18, and 22 at relatively equal prevalence. Discussion: Review of our data indicates a higher prevalence of chromosomal mosaicism identified through conventional cytogenetic methods across various specimen types compared to existing literature. Furthermore, our limited genomic sequencing data suggests that conventional cytogenetic technologies may detect chromosomal mosaicism more frequently than genomic technologies. These findings underscore the importance of employing karyotyping and FISH for the detection of chromosomal mosaicism, particularly at low levels, which may be missed by genomic sequencing. Additionally, a thorough examination of clinical phenotypes can enhance the suspicion of mosaicism, ultimately enhancing diagnostic rates.

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  Effect of Social Determinants of Health on Clinic Visit Attendance in Patients with Hemophilia

  Shailly Gaur; Brian Lee PhD, MPH; James Anderst MD, MSCI; Katie Foote LSCSW, LCSW, OSW-C; Andrea Bradley-Ewing MPA, MA; and Shannon L. Carpenter

  Background Social determinants of health (SDOH) create barriers to seeking care regularly, especially for patients with chronic disease. Patients with moderate-severe hemophilia A and B (factor 8 and 9 deficiencies respectively) have a life-long higher risk of bleeding and require chronic therapies. Specialized care is offered through hemophilia treatment centers (HTCs); however, these can be difficult to access for some individuals. Previous SDOH research in this patient population has been limited; therefore, it can be difficult to identify the barriers to care that exist. There is a need to examine SDOH more thoroughly to create patient-directed interventions to improve access to care. Objectives To identify common SDOH affecting patients with moderate-severe hemophilia and determine how each impacts clinical utilization within a single HTC. Methods A retrospective chart review of patients age < 18 years old with a diagnosis of moderate or severe hemophilia A or B seen at Children’s Mercy Hemophilia Treatment Center over the last five years. Dependent variables included no-show visits, which were any missed visit since the patient established care, and missed yearly comprehensive visits, of which non-parametric distributions were calculated. Rates were standardized to an assumed 10-year follow-up period and then compared across independent variables including race, ethnicity, language spoken, insurance type, rural vs urban home, food insecurity rate, poverty level, distance to an ER and to the HTC using the Kruskal-Wallis and Wilcoxon rank-sum tests, where appropriate. Significant findings were determined using a p-value < 0.05. Results Patients with the following SDOH had a statistically significant difference in rates of no-show visits: distance >60min from the HTC (p=0.009), urban vs rural home county (p=0.033), race of patient (p< 0.001), and insurance status (p=0.007). [Figure 1] Further demographic data and analysis included with confidence intervals provided in Fig 1. Conclusions The rate of no-show visits was most affected by patient race, insurance type, distance from HTC, and urban vs rural living conditions. No statistically significant correlations existed within the yearly comprehensive visits, which may be indicative of the shared importance of keeping regularly scheduled appointments between patient and provider when caring for a chronic disease. Interestingly, though previous data in this field has demonstrated rurality as a limitation to care, these findings suggest that an urban setting closer to the HTC presented more of an issue. These findings also help support the benefits of outreach clinics in providing specialized care directly in rural environments, likely reducing no-show rates in this population. This may inspire a similar approach to localized outreach within the urban neighborhoods affected by SDOH limitations to offer clinics where patients are most vulnerable.

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  Engineering A Novel Treg Population to Control Autoimmune Diabetes

  Sofia Colon Guzman, Elly Puckett, Ryan T. Fischer, and Mary Markiewicz

  Purpose Type 1 diabetes (T1D) in an autoimmune disorder where T cells attack  islet cells, which are the pancreatic cells responsible for insulin production. T1D affects about 1 in 500 children in the United States and is one of the most common chronic diseases in pediatrics. Currently, insulin is the most effective treatment for T1D However, it does not change the underlying disease, and patients still experience many complications throughout their lifetimes. With a significant increase in the prevalence of T1D in children and adolescence in the past two decades, it’s important to explore therapies that alter the immune response as a possible way to reverse or even prevent the progression and development of this disease. One approach being investigated is to use regulatory T cells (Tregs), which can suppress the function of autoreactive T cells, as treatment for autoimmune disease. However, using a patient’s own naturally occurring Tregs (nTregs) as therapy poses several challenges. Therefore, we developed a novel way to generate human engineered Tregs (eTregs) from conventional T cells (Tconvs) by expressing both FOXP3 and HELIOS in both CD4+ and CD8+ Tconvs. We hypothesize that these novel eTregs will be as, or more, effective in their suppressive abilities against islet-specific effector T cells and be more stable under inflammatory conditions compared to naturally occurring Tregs. Methods We isolated CD8+ T cells from healthy human donors through negative selection using magnetic beads. From these cells we created cytotoxic T cells (Tconvs) through lentiviral transduction of a vector that expressed a TCR specific for an islet-specific antigen (IGRP) presented in HLA-A2:01 and mCherry as a fluorescent marker of transduction. The presence of IGRP-specific TCR was confirmed using dextramer staining. These Tconvs were co-cultured with BetaLox5 cells, an immortalized human cell line derived from islet cells. The response of the CD8+ Tconvs was determined by measuring effector cytokine release. We also created autologous natural Tregs (nTregs) and tested the ability of these cells to reduce the CD8+ Tconv response against BetaLox5Unpaired T test analysis was used to measure the statistical difference in cytokine production between co-culture conditions. Summary of Results IGRP-specific T cells responded to the human islet cell line BetaLox5 in vitro, demonstrated by elevated IFN-γ and TNF- production after co-culture. This response was decreased when nTregs were present in co-culture, as the amount of IFN-γ and TNF- in co-culture supernatant was significantly lower. Conclusions We were able to create a model to test the immunosuppressive capacity of Helios+FOXP3+ eTregs compared to nTregs against islet-specific autoreactive T cells. We also showed that nTregs decrease the response of these cytotoxic T cells when co-cultured with BetaLox5 cells. We are now comparing the immunosuppressive ability of our eTregs to nTregs in this assay, as well as comparing their stability under inflammation.

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  Viral Detection in Anterior Nasal Swabs Versus Nasopharyngeal Swabs in Children

  Nicole Neeley, Abby Kietzman, Rangaraj Selvarangan, Dithi Banerjee, Jennifer Goldman, and Jennifer Schuster

  Background: Respiratory viruses are a significant cause of pediatric illness and healthcare utilization. Diagnostic testing for respiratory viruses is generally performed using nasopharyngeal (NP) specimens obtained by trained medical staff, limiting testing to medical settings. Evaluating additional sampling methods in children, such as anterior nasal swab (NS) specimens may expand access to diagnostic testing and aid public health surveillance. Methods: Eligible children hospitalized at Children’s Mercy Hospital in Kansas City who had a standard of care NP specimen collected for nucleic acid amplification testing for respiratory viruses were enrolled. Research NS specimens were obtained through self, caregiver, or staff collection. Specimens were tested on QIAstat-Dx-Analzyer using QIAstat-Dx Respiratory SARS-Cov-2 Panel and included: adenovirus, seasonal coronavirus (229E, HKU1, NL63, OC43), SARS-CoV-2, human metapneumovirus (hMPV) A+B, influenza A/A H1/A H3/A H1N1/pdm09, influenza B, parainfluenza virus 1/2/3/4, rhinovirus/enterovirus (RV/EV), and respiratory syncytial virus (RSV) A+B. Statistical analysis for sensitivity with 95% confidence intervals was calculated with NP as the gold standard. Further sub-analysis evaluating time to NS collection and test results (NP specimens as time zero and NS specimens grouped from 1-24 hours, 25-48 hours, and 49+ hours) was performed. Pairs with both NP and NS specimens having viruses detected or the same virus(es) detected were considered completely concordant. Specimens with multiple viruses detected on NP swab but only a single virus detected on NS swab, or vice versa, were considered partially concordant. Specimens with one virus detected on NS or NP and none detected on its pair were considered discordant. Results: One hundred and forty-seven pairs, each including one NP and one NS specimen, were obtained. Of the 147 pairs, 114 (77.5%) had complete concordance – 86 (58.5%) had viruses detected and 28 (19%) had no viruses detected. Fourteen (9.5%) pairs were partially concordant, and 19 (13%) were discordant. Sensitivity of NS specimens collected within 48 hours of their NP pair was ≥80% for all viruses except seasonal coronavirus (sensitivity 42.9%) (Table 1). NS specimens for adenovirus, influenza, parainfluenza, RSV, and SARS-CoV-2 were 100% sensitive when collected within 24 hours of NP specimens. Conclusion: Overall, NS are a potential alternative method for respiratory virus detection in the pediatric population. This less invasive collection method allows for broader use outside of medical settings, including respiratory virus surveillance in community settings. Future studies with closely time-matched NS and NP collection are needed to evaluate individual virus type detections.

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  A Case of Heterotaxy and Common Atrioventricular Canal with Bradycardia

  Mohamed Aashiq Abdul Ghayum, Jenna Schermerhorn, Hayley S. Hancock, Kelsey Brattrud, Melanie Kathol, and Maria Kiaffas

  Background: Heterotaxy-polysplenia syndrome (otherwise known as left atrial isomerism) should be suspected in the presence of complete atrioventricular canal defect (CAVC) with interruption of the inferior vena cava (IVC), atrioventricular block (AVB), and viscero-cardiac heterotaxy. The prognosis remains dismal for the fetus with such entity, especially in the presence of major structural heart disease and high-grade atrioventricular block. Early diagnosis, close follow up, and appropriate delivery planning, allows for effective stabilization of the baby after birth and might improve survival. Methods: A 26-year-old mother at 26 weeks gestational age was referred for cardiac evaluation of cardiomegaly, suspected CAVC and bradycardia. Maternal SSA and SSB antibodies were negative. Fetal echocardiogram showed moderate cardiomegaly, bradycardia with 3° AVB with ventricular rate of 64 beats per minute. Anatomy was consistent with heterotaxy {S/A,D,S}, hypoplastic left atrioventricular valve, unbalanced, right-dominant CAVC, dysplastic pulmonary valve, interrupted IVC with azygous continuation to a persistent left superior vena cava draining to a dilated coronary sinus. Partial anomalous pulmonary venous connection and coarctation of the aorta were suspected. Biventricular function was low normal with ventricular non-compaction. Ductus venosus Doppler was notable for a-wave reversal. Umbilical artery and middle cerebral artery waveforms were normal. Biweekly follow-up revealed worsening extracardiac Dopplers and decreasing ventricular function. Results: Given the prematurity, bradycardia, complex cardiac anatomy, non-compaction and ventricular dysfunction, prognosis was considered unfavorable. An integrated consult involving fetal cardiology, neonatology, Electrophysiology (EP) and Palliative care teams was undertaken. The family was counseled for guarded prognosis and high risk for demise, need for postnatal permanent pacemaker and surgical repair leading to a single ventricle pathway with possibility for heart transplant. A 2.79 kg female was delivered by c-section at 35 weeks 5 days; Apgar score was 4,4,and 8. The newborn was immediately transferred for placement of temporary pacing wires with subsequent transfer to the cardiac intensive care unit for stabilization and further management. Coarctation repair, PDA ligation and permanent pacemaker placement were performed at 4 weeks of age. Progressive biventricular dysfunction, bilateral outflow tract obstruction and pacemaker dependency resulted in transplant listing of the patient with a successful orthotopic heart transplantation taking place at 4 months of life and has continued to do well on follow up. Conclusions: Heterotaxy polysplenia syndrome should be suspected in cases with CAVC with interruption of the IVC, and AVB. The presence of major structural heart disease and high-grade AV block carries a guarded prognosis, with survival to discharge from the hospital after delivery at term or near term reported to be less than 50%; in cases of prematurity, survival is expected to be even lower. In our patient, early diagnosis, appropriate counseling, close follow-up and meticulous delivery planning allowed successful perinatal stabilization with timely pacing and effective supportive management. Timely listing and eventual heart transplantation resulted in the survival of this patient.

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  Duration of Labor and Umbilical Artery Acidosis in Critical Congenital Heart Disease

  Sarah Gwazdacz, Teresa Nguyen, Henry Yeh, Mary T. Donofrio, Timothy Bennett, and Amanda McIntosh

  • Background (83 words): Standard delivery protocols for most prenatally diagnosed CCHD is induction of labor at 39 weeks with aims of a vaginal delivery (VD) near a tertiary care center. There is no benefit to planned Cesarean delivery (CD) over VD for most infants with CCHD. However, longer durations of labor (DOL) in CCHD have been described as a risk factor for umbilical artery (UA) acidosis. We aim to describe the relationship between DOL and UA pH and neonatal outcomes in those with prenatally diagnosed CCHD. • Methods (150 words): Retrospective chart review of prenatally diagnosed with CCHD born at Children’s Mercy from 2012 – 2023. Inclusion criteria was CCHD defined as anticipated neonatal intervention or prostaglandin dependence, single ventricle (SV) circulation, or risk of hemodynamic instability with placental separation. Excluded fetal demise, multiple gestations, prematurity, post-maturity, and comfort cares. Divided subjects into 3 groups: those who had VD, CD after a trial of labor (TOL), or CD without a TOL. The primary outcome was UA pH. Secondary outcomes were delivery room intubation, perinatal brain injury, and peak lactate, cardiac arrest, death, or inotropic support in the first 24 hours of life. Collected demographic and clinical information for the maternal-fetal dyad. Divided CCHD diagnoses into 4 groups based on SV versus biventricular anatomy and the presence of systemic outflow obstruction. Welch 2-sample test or ANOVA were used for inter-group comparisons. For associations, multivariable linear regression modeling was performed. • Results: (150 words) Analyzed 201 VD, 32 CD after a TOL, and 90 scheduled CD without a TOL patients. Between the groups, there was no difference in birth weight (BW), gestational age (GA), intrauterine growth restriction (IUGR), and UA pH. Mothers with planned CD were older and delivered fetuses with higher rates of genetic syndromes. On univariate analysis, DOL in VD group was associated with lower UA pH (estimate -0.0006707 (95% CI: [-0.00130, -0.00005], P-value: 0.037). This remained significant on multivariable analysis controlling for GA, BW, hydrops, genetic syndromes, and IUGR (P-value = 0.011). Looking at CCHD subgroups, DOL and UA pH only had a significant association in neonates with SV anatomy and systemic obstruction (P-value= 0.009). DOL and lactate had a significant relationship on univariate (estimate 0.01479 (95% CI: [0.00307,0.02651], P-value= 0.014) and multivariate analysis (p-value = 0.015). There was not a significant relationship between DOL and other secondary outcomes. • Conclusion (51 words) In this single center retrospective study of fetuses with CCHD, longer duration of labor was associated with higher neonatal lactate levels. It was associated with lower UA pH in neonates with single ventricle anatomy and systemic obstruction. This may be a modifiable risk factor in certain subsets of prenatally diagnosed CCHD.

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  OCD Lesions of the Lateral Femoral Condyle and the Impact of the Location on Recovery

  Catharine Kral, Joshua Cummings, Ellie Helton, Shannon Margherio, Brian S. Harvey, and Kevin Latz

  Descriptive study based on Zhou, Liang, et al. we categorized the LFC OCD lesions into weight bearing and non-weight bearing lesions to assess clinical and radiographic variables and evaluate the need for progression to operative management.

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  Discrepancy Between Hyaluronic Acid Levels And Mri-Based Measurements Of Hepatic Fat And Fibrosis

  Daniel Aaron Borman, Rachel Chevalier, Jonathan Wagner, Michele T. Pritchard, Sherwin S. Chan, Nathan S. Artz, Johnston Fite, Yoon Cho, Valentina Shakhnovich, Veronica Williams, and Voytek Slowik

  Introduction Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children in the United States and, when left untreated, can progress to liver fibrosis. Clinicians currently utilize imaging and biopsy to assess fibrosis in this patient population as there is no validated serum biomarker available for detecting fibrosis. Previous research suggests that serum hyaluronic acid levels are predictive of hepatic fibrosis in children with MASLD. Methods Retrospective data were obtained from the Children’s Mercy Hospital Liver Lab study. Pediatric subjects with both hyaluronic acid (HA) samples and MRI evaluation within a month were identified and included for evaluation. Hyaluronic acid was evaluated via an ELISA-like assay. Measurements of hepatic fat fraction (HFF) and elastography were obtained via averaged MRI region of interest evaluation . SPSS software was utilized to assess correlation between anthropometric measurements, hyaluronic acid, and MRI data, including both HFF and elastography. Results A total of 59 patients with 98 unique data points were identified for analysis. Moderate correlations were found between BMI z-score and HFF (r=0.36, p=0.002) and elastography (r=0.47, p<0.001). No statistically significant correlation was identified between HA and BMI z-score (r=-0.09, p=0.348), HFF (r=-0.05, p=0.633), or elastography (r=-0.20, p=0.051). Conclusion In contrast to previous literature, this study did not demonstrate a statistically significant correlation between hyaluronic acid levels and MRI-based measurements of hepatic fat or fibrosis. Further research is needed to identify biochemical markers to predict fibrosis in children with MASLD.

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  A Unilateral Myopic Shift Secondary to Sturge-Weber Syndrome Results in Refractive Amblyopia of the Fellow Eye in a Pediatric Patient

  McKenzie Stewart and Christina Twardowski

  A 4-year-old patient with unilateral glaucoma secondary to Sturge-Weber Syndrome causes a myopic shift. The fellow healthy eye maintains high hyperopia resulting in anisometropic refractive amblyopia, requiring occlusion therapy. It is well documented that a glaucomatous high IOP causes an expansion of the globe due to excessive plasticity of collagen fibers in pediatric eyes. The elongated axial length induces myopic shifts. In this patient, the myopic shift in her glaucomatous eye resulted in a unilateral high hyperopic refractive error in the fellow eye with normal ocular health. This anisometropia is enough to cause amblyopia in the hyperopic eye. In past appointments, the patient demonstrated equal visual fixation with the 10BD prism test. Since equal fixation was previously found, no amblyopia therapy was initiated. Now that the patient can verbalize optotype acuity, a moderate amount of amblyopia was found warranting additional treatment. The mainstay treatment for moderate unilateral amblyopia is patching therapy or atropine penalization. As the patient has already been in the correct optical correction since 11 months of age, it can be assumed she has reached her maximum vision improvement from spectacles alone. The glasses prescription has been monitored closely since the initial visit and has remained stable. Based on the patient’s refractive error, depth of amblyopia, and family’s preferences, patching the left eye 2 hours a day was initiated. In this case, the eye without the initial pathology developed an amblyogenic reduction in visual acuity. With the lifelong risk of glaucomatous vision loss, it is important to maximize visual potential in the healthy eye of our patient while they are still in their vision development period. In the setting of ocular pathology in pediatric patients, it is important to understand the secondary impacts that could occur during the vision development period.

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  But, It's Just a UTI

  Gillian Long

  IgA Vasculitis is a commonly seen presentation in the pediatric population. The constellation of symptoms typically includes purpuric rash, joint pain, abdominal pain and hematuria. This 12 year old female was seen by her pediatrician for rash on her legs, shortness of breath, cough and night sweats that all started around 2 months ago. Additionally, a 25 pound weight loss was noted over the past year. The rash appeared as nonblanching purpura on her lower extremities, lending suspicion to IgA Vasculitis. She was first treated for UTI with cefuroxime, and then treated with steroids. Urinalysis showed persistent hematuria and she was referred to nephrology. At her first visit, she was sent to the Emergency Department for tachypnea and increased work of breathing. Baseline labs showed normal electrolytes and kidney function, elevated inflammatory markers (CRP of 19.1 and ESR of 26), and mild leukocytosis. Urinalysis showed 3+ blood and 3+ protein. Chest CT demonstrated extensive bilateral peribronchial cuffing, multifocal bronchiectasis, scattered upper lobe airspace disease, and a diffuse treein-bud nodular pattern. Initial differential included vasculitis, disseminated tuberculosis or fungal infection, or primary pulmonary disease. Ultimately, multiple specialty services were consulted. Rheumatology workup included ANCA vasculitis panel, ANA, C3, C4 and IgG levels, all negative. Nephrology obtained a kidney biopsy, which was consistent with IgA Nephropathy. Infectious Diseases requested multiple AFB sputum cultures and gastric aspirates, along with Quantiferon Gold and Fungal cultures, with the only positive finding being Pseudomonas aeruginosa growth in the sputum. Lastly, Pulmonology recommended sweat chloride tests, both positive; so whole exome sequencing was obtained and showed 2 pathogenic mutations in the CFTR gene, confirming a diagnosis of cystic fibrosis. The final diagnosis was Cystic Fibrosis with chronic Pseudomonas infection and secondary IgA vasculitis and Trikafta. Her PFTs continue to improve and she has not re quired readmission to the hospital since the nephritis. She was treated with pulse steroids, IV antibiotics and eventually started on Cellcept and diagnosis was made. While this patient did have a secondary IgA Vasculitis, not all of her symptoms were typical. Severe lung involvement is uncommon in IgA Vasculitis and requires additional workup. Additionally, while cystic fibrosis is well diagnosed with newborn screening, it should be considered in appropriate clinical scenarios when newborn screening was not obtained.

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  Terminal Ileal Intubation In Retroflexion In A Pediatric Patient

  Lakshmi Kunam, Antonia Fernandez Ovalle, and Thomas M. Attard

  Background: Terminal ileum (TI) intubation is integral to complete diagnostic ileocolonoscopy in children. It is necessary to determine terminal ileal involvement in patients with a broad spectrum of pathologic processes. In some cases the standard method of intubation does not lead to success and retroflexion is needed. Here we describe the case of terminal ileal intubation in retroflexion on a 14 year old female. Case description: 14 year-old female patient with a past medical history of chronic abdominal pain, NAFLD, anxiety, vulvovaginitis, lichen sclerosus, depression, constipation, delayed menses, and GERD who was admitted for 2 weeks of escalating symptoms and referred for endoscopy and colonoscopy to investigate potential lower intestinal etiologies. During colonoscopy, the 38 - EC 38 i10L Pentax scope was used. Intubation of terminal ileum was therefore necessary for completeness of exam but was deemed technically unfeasible after three attempts with pullback maneuver (because of inferiorly directed ileocecal valve). Ileal intubation was accomplished by careful retroflexion in the cecum with intubation upon scope withdrawal followed by advancing forward into the last 10 – 15 cms of TI. Discussion: Retroflexion for ileal intubation has been described during double balloon Enteroscopy and is useful when the ileocolic angle cannot be reduced sufficiently by pull-back of the overtube balloon or when the ileocecal valve is very backward facing. These issues with anatomy, position, and shape of the ileocecal valve are present during ileocolonoscopy as well. However, a maneuver with retroflexion is rarely used for concerns of perforation. Intubation of the terminal ileum in retroflexion has been done in adults and has been termed the Moonsault manuevar. To the best of our knowledge retroflexion for ileal intubation has not been documented in children. Conclusion: Our experience demonstrates that terminal ileal intubation in retroflexion can be done safely in the pediatric population. Assessing the outcomes of this in other similar patients will assist in determination of further guidelines of this maneuver and optimal patients for safe execution of this maneuver.

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  An Early Successful Hematopoietic Stem Cell Transplant (Hsct) For A Boy With Ipex Syndrome

  Ali H. Alnajim and Salman Aljubran

  Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare inborn error of immunity. It affects about one in every 1.6 million people. It is caused by mutations in the forkhead box P3 (FOXP3) gene on chromosome Xp11.23. FOXP3 is a vital regulator of T cell development and function. Dysfunctional FOXP3 allows the hyperactivation of T cells, resulting in skin rash, enteropathy, diabetes, thyroiditis, hemolytic anemia, and thrombocytopenia. The classic clinical presentation is intractable diarrhea, growth problems, dermatitis, and autoimmune endocrinopathy. Case Description: A 4-week-old male was transferred to our hospital’s NICU due to respiratory distress and feeding difficulties. Neurology was consulted due to hypotonia and swallowing difficulties. Neurology recommended genetic testing. Exome sequencing identified a hemizygous pathogenic variant in FOXP3, consistent with a diagnosis of IPEX syndrome. Immunology, Endocrine, Dermatology and GI teams were consulted. The transplant team was involved. Immune workup was normal including normal FOXP3 protein expression in the Treg cell. He had myeloablative chemotherapy followed by matched unrelated donor stem cell transplant at the age of 4 months. He was discharged from hospital at the age of 6 months. Discussion: IPEX syndrome should be considered in young males with severe intractable diarrhea and other autoimmune endocrinopathies especially Insulin dependent diabetes mellitus (IDDM). Sequencing of the FOXP3 gene should always be carried out to look for mutations even in the face of normal FOXP3 protein expression in the Treg cell. A timely diagnosis is essential to offer HSCT in this potentially fatal disorder.

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  Elevated Tryptase Level Identifies A Case Of Hereditary Alpha Tryptasemia

  Ali H. Alnajim and Salman Aljubran

  Introduction Hereditary alpha tryptasemia (HaT) is a rare genetic disorder characterized by elevated serum tryptase levels due to duplication or triplication of the TPSAB1 gene. Affecting 6 to 8 percent of the population, HaT presents with diverse symptoms, including idiopathic anaphylaxis, skin rashes, and gastrointestinal issues. This report highlights a case that underscores the complexities and diagnostic challenges of HaT. Case Description A 4-year-old male presented with recurrent skin rashes and gastrointestinal symptoms following ingestion of certain foods, despite negative allergy tests. Persistent symptoms led to further investigations, revealing elevated tryptase levels of 10.3 ng/ml, 12.1 ng/ml, and 8.3 ng/ml over several months. The c-Kit D816V mutation test was negative, prompting genetic testing for TPSAB1 CNV, which confirmed HaT. Discussion The diagnosis of HaT in this patient illustrates the need for a comprehensive diagnostic approach in individuals with recurrent anaphylaxis and unexplained allergic reactions. Elevated tryptase levels served as a crucial biomarker, guiding genetic testing and confirming HaT. This case highlights the importance of early identification and management of HaT to prevent severe systemic reactions. As clinical understanding of HaT evolves, integrating genetic testing into routine practice will enhance diagnostic accuracy and patient care.

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  Increased Red Cell Distribution Width (RDW) is associated with culture positive sepsis and with increased need of escalation in respiratory support in very low birth weight infants more than seven days of life undergoing sepsis workup secondary to vitals instability in the form of multiple episodes of true apneas or bradycardia and desaturations associated with apnea

  Kedar Tilak, Aashka Patel, and Anna Zylak

  Background Apnea of prematurity is nearly universal among very low birth weight infants (VLBW). In VLBW infants, changes in clinical status usually occur due to sepsis or non-infectious causes and it is challenging to differentiate between the two. We as clinicians use irregularities in vital signs as an early warning sign of sepsis to facilitate early treatment and improve patient outcomes. Adults have used RDW as a marker of worsening respiratory status and mortality from acute respiratory distress syndrome (ARDS). In this study, we seek to investigate elevations in Red Cell Distribution Width (RDW) as markers for culture positive sepsis and need for escalation of respiratory support in VLBW neonates. Methods We did a retrospective chart review using the Electronic Medical Records (EMR) of VLBW infants (< 1500g) admitted to the Neonatal Intensive Care Unit (NICU) of a community hospital over 3 years. We included all babies who had True apnea (apnea > 20 seconds) or apnea with bradycardia and desaturations, after day seven of life and had CBC tests sent and were being managed for presumed late onset sepsis secondary to this vital sign instability. Other demographic data was gathered and tabulated. The data was analyzed to check for association between increased red cell distribution width (RDW) and need for escalation of respiratory support. Escalation in respiratory support included an increased need of assisted ventilation to support breathing. We also looked at positive blood / urine cultures and RDW values. Results 50 babies matched our inclusion criteria. 31 babies had a positive blood /urine culture. 21 of the 31 had elevated RDW which was statistically significant at p< 0.05 (Table1), hence showing that positive culture late onset sepsis had elevated RDW. Also, we saw increased need for escalation in respiratory support amongst culture positive babies with an elevated RDW at p < 0.05 (Table 2). Conclusion We conclude from this, that elevations in RDW is a marker for VLBW babies needing escalation in respiratory support. Elevations were also seen in culture positive sepsis. More studies need to be done as most of the available data is in adults. We can look more associations in babies with RDS (respiratory distress syndrome) and predict respiratory distress and for early interventions and better outcomes.

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  Intraoperative Status Asthmaticus in a Morbidly Obese Preteen Undergoing Concomitant Vertical Sleeve Gastrectomy and Orthotopic Liver Transplant

  Abigail Pint, Neal Campbell, and Preethi Tumati

  10-year-old morbidly obese male with cirrhotic ESLD secondary to vertically transmitted Hepatitis C presented for liver transplantation and concomitant vertical sleeve gastrectomy. Other history included moderate persistent asthma, OSA, and presumed HPS with baseline SpO2 of 94%. Induction was smooth; intubation with an armored ETT was easy. During invasive monitor placement, bronchospasm worsened SpO2. Continuous albuterol nebulization provided reasonable reversal, and all stakeholders agreed to proceed. Postoperative course was complicated by status asthmaticus and dramatic extubation on POD3 when patient bit and kinked armored ETT. To date, patient has good graft function and a 16% reduction from his peak BMI.

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  Variables affecting neurodevelopmental outcome in infants with critical congenital heart disease

  Elizabeth Loughman, Marcie G. Files, and Julie Weiner

  Background: The mortality of cardiac conditions in infancy is improving with advances in surgical planning and medical management. Neurologic morbidity remains significant. Clinically correlating an infant with their neurologic exam, MRI/EEG, and subsequent developmental testing remains a challenge. Counseling regarding neurologic outcomes after cardiac intervention is difficult due to the wide range of findings that can sometimes be clinically irrelevant. Purpose: The goal of this study is to identify factors associated with poor neurodevelopmental outcomes in infants with critical congenital heart defects (CCHD) as assessed by the Bayley Scales of Infant and Toddler Development Edition IV (Bayley). Methods: This is a retrospective single site study performed at a freestanding children’s hospital with delivery services. Neonates were inborn or admitted to the neonatal/cardiac intensive care units following diagnosis of CCHD over a 5-year period who required cardiac surgical procedures during their initial hospital stay. Patients were sampled from databases in the heart center and the Children’s Hospital Neonatal Consortium. Neonates were stratified by single vs biventricular repair and Norman category of heart defect (A, B, or C). Primary outcomes included neurologic exam, MRI, and EEG at discharge and 12- and 24-month Bayleys. Results: 383 neonates were included in analysis. 57.2% were male with an average gestational age of 39 weeks and average birthweight of 3.2kg. The average length of stay was 36 days. Of the entire sample, 36.3% had Bayleys performed at 12 months and 25.8% at 24 months. 38% of the entire sample underwent a single ventricle repair. 39% were classified as Norman A, 41% Norman B, and 19% Norman C. 40% of Bayleys were abnormal, with highest impairment in gross motor skills and expressive language. Of the 145 infants with EEGs, 17% showed seizures or focal slowing. Of these abnormal EEGs, approximately 45% had an abnormal Bayley. Of the 146 infants with MRIs, 58% showed ischemia, infarct, atrophy, stroke, or hemorrhage. The odds in favor of an abnormal Bayley at 12 months was 3.11 times higher among infants with abnormal MRIs (95% CI 1.22-7.94, d= 0.63). 6.5% had an abnormal neurologic exam, most commonly hypotonia. Of these abnormal neurologic exams, 73% had abnormal 12-month Bayleys and 87.5% had abnormal 24-month Bayleys. Conclusion: Abnormal neurologic exams, MRI, and EEG at discharge can be associated with abnormal Bayleys in childhood. This helps in counseling families and providing long term neurodevelopmental follow up.

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  A Genomics Driven Human Induced Pluripotent Stem Cell Model of Infant ALL – Updates on Hematopoietic Differentiation

  Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Priyanka Kumar, Bradley Thornton, Molly Leyda, Midhat Farooqi, Erin Guest, Jay L. Vivian, and John M. Perry

  Acute lymphoblastic leukemia in infants (iALL) is a high-risk subtype of childhood leukemia, with poor survival outcomes despite intensive therapies. Rearrangement of KMT2A (KMT2A-r) occurs in 70% of cases and is associated with chemotherapy resistance, early relapse, and rapid leukemic progression, all of which contribute to poor survival outcomes. The most common KMT2A-r in iALL is KMT2A::AFF1 (MLL::AF4), derived from t(4;11)(q21;23). This KMT2A-r generates a driver fusion oncogene which leads to epigenetic dysregulation of target gene transcription. Infant ALL’s cell of origin is thought to be a very early hematopoietic precursor, with transcriptomic studies of iALL blasts showing similarities to hematopoietic stem and progenitor cells (HSPCs), multipotent progenitors and early lymphoid progenitors (ELPs). Unfortunately, research into this devastating disease has been hampered by the lack of a representative model of iALL Attempts at creation of an iALL models have led to a variety of results including myeloid neoplasms, lymphomas, myeloid/lymphoid hyperplasia or leukemia, mature B cell neoplasias, or in one instance, a B-lymphoblastic leukemia with prolonged latency. Because of these failures, much remains unknown regarding how KMT2A::AFF1 transforms early hematopoiesis or how it alters the severity of the disease. To understand the developmental state of the cell of origin and progression of iALL, we have created a highly controlled human inducible pluripotent stem (iPS) cell model of KMT2A::AFF1 iALL. Specifically, we engineered human iPS cell lines with doxycycline regulatable expression of KMT2A::AFF1 fusion and have confirmed expression of the KMT2A::AFF1 transcript. Through directed differentiation we have also produced functional HSPCs from iPS cells with multilineage differentiation capacity, as evidenced by differentiated cells being transcriptionally similar to erythrocytes, megakaryocytes, and monocytes. The iPS cells are currently being guided through lymphocyte differentiation. This model has allowed us to recapitulate hematopoietic ontogeny with the ability to control iALL induction at specific developmental stages. We are using single cell genomics to investigate transcriptomic changes during hematopoietic differentiation of our KMT2A:AFF1 iPS cell line. Through this research we expect to discover the genomic and epigenetic landscape and cellular evolution of iALL with the long-term goal to uncover targets specific to iALL for the development of new therapies.

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  "Ghosts in This Country": Pediatric Caregiver Perspectives on Immigration Status in the Healthcare Setting

  Anik Patel, Ali Fowler, Juan Farias Torres, Ana Contreras, Claudia Zepeda, Estefania Bazan, John Cowden, Frances Turcotte Benedict, Jennifer Watts, and Kimberly A Randell

  Background: There are approximately 11.4 million undocumented immigrants (UI) in the United States. Immigration status (IS) is a unique social determinant of health that directly and indirectly impacts health and healthcare access. There are gaps in our understanding about how IS impacts health, particularly because it is not frequently discussed in the healthcare setting. This study expands our understanding of immigrant caregiver perceptions about discussing IS in the healthcare setting and provides insight into specific needs that we may not be currently addressing. Methods: Setting: ED or Spanish-speaking majority pediatric clinic at Children's Mercy Inclusion criteria: Caregivers who are 18+, identify as Latin/Hispanic, are Spanish-speaking, and do not have a social security number Exclusion criteria (determined by study team): Caregivers of critically ill patients or patients undergoing sensitive exam, caregivers with developmental delays Recruitment: Potential participants identified by Spanish preference on clinic schedule/ED tracking board. Confidentiality was stressed and a private setting was offered for interviews after screening/enrollment Data Collection: Demographic data was collected using a REDCap-based survey. 20 interviews were conducted from April 7, 2023 to February 28, 2024. The interview guide was developed by iterative repetition by a diverse author group. All interviews were conducted in-person with bilingual individuals. Remuneration: $50 gift card and list of resources in Spanish/English Data Analysis: Interviews were recorded using an audio recorder and then transcribed into Spanish/English. 3 independent coders analyzed de-identified transcripts using an inductive approach. Results: Theme 1: UIS negatively impacts multiple aspects of health, but many people do not connect UIS with health. Theme 2: There are many perceived barriers to disclosure of UIS, but varied perspectives on whether providers should discuss IS in the healthcare setting. Theme 3: There are many barriers to resource utilization for UI. Theme 4: There are a variety of needs in the community and many UIS seek these resources from varied places, but many also don’t know where to go for information. Theme 5: There are things that medical teams can do to facilitate resource utilization and discussion about IS in the healthcare setting, but one size does not fit all. Conclusion: Caregivers offered perspectives on the impact of UIS on health and identified barriers to and facilitators of discussing immigration status while in healthcare settings. Universal provision of resource information may more effectively support families with caregivers who are undocumented immigrants

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  System-based integrated comprehensive simulation program in pediatric residency education: our institutional experience

  Mahmoud Jaara, Jenn M. Zimmerman, Jean Ann Hutton, Nancy Joseph, and Maritza Plaza-Verduin

  Background: Simulation provides the opportunity for learners to bridge the gap between evidence-based theoretical knowledge and clinical practice experience. Residency programs often utilize simulation to expose the learners to various patients who are presenting in extremis in a safe environment. This empowers the trainee by providing them with tools and experiences to enhance their pediatric education. Simulation is also utilized to practice non-technical skills like team dynamics and communication in a psychologically safe setting. Despite the widespread use of simulation in pediatric residency programs, there remains a gap in standardization. In response to this gap, we sought to create a comprehensive, system-based curriculum (clinical skills and clinical scenarios) that integrated simulation and system-based traditional didactic learning. Methods: Our methodology embraced a comprehensive approach, emphasizing essential topics and clinical skills pertinent to each system through didactic lectures during our academic half-day sessions. Starting with an 18-month calendar outlining didactics, we meticulously planned a corresponding simulation calendar. This calendar included a 3-4-hour session in the simulation center every six weeks. During that session, residents would participate in clinical simulation scenarios (both emergency and non-emergency) and clinical procedures skills stations. Along with these half-day sessions, we incorporated monthly in situ simulations during day and night shifts involving multi-disciplinary team members, including nurses and respiratory therapists. A dedicated Simulation Task Force comprising faculty and fellows was convened. Simulations were meticulously aligned with the content outline provided by the American Board of Pediatrics (ABP) and ensured adherence to Accreditation Council for Graduate Medical Education (ACGME) task lists. Evaluation of simulation activities was conducted through post-surveys gauging participants' comfort levels across various clinical scenarios. Each clinical Simulation scenario has to cover vital components: medical critical actions and team dynamics and communications skills, acquired skills, and pattern recognition at the end of the sim. Results: Our review of resident simulations conducted over the past year yielded insightful findings. In our post-surveys, 100% of the respondents stated that the integrated simulations reinforced their knowledge or allowed them to gain new knowledge or skills and that the experience improved their confidence in their own knowledge or skills. Over 50% of the participants indicated that they felt the skills they practiced would apply to their jobs and help them provide safer patient care. Conclusion: By integrating simulation within a system-based curriculum, our approach offers a structured pathway to enhance pediatric residency education, fostering a more standardized and effective learning experience. Reviewers comment(s) regarding your abstract: This abstract describes the integration of simulation to didactic learning during academic half day sessions, which should allow residents the ability to apply what was learned in a safe, simulated environment. While it is helpful to recognize that residents reported that the simulations allowed application and would create a safer environment, were other higher level metrics collected? Perhaps metrics related to resident performance in the simulations or safety related data before and after the restructuring of the curriculum? The abstract was confusing as I was unable to tell why this study was performed (no needs assessment), who performed the simulations, what simulations were performed, and why the simulations were done. In the future, abstract would benefit from more clarity or for a graph/image to describe the intervention further.

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  Association Between Neighborhood Opportunity and Youth Mental Health Emergency Department Visits

  Shelby Chesbro, Matt Hall, Adrienne DePorre, Molly Krager, Laura Plencner, Shayla Sullivant, and Henry T. Puls

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  Variables affecting neurodevelopmental outcomes in infants with critical congenital heart disease

  Elizabeth Loughman, Marcie G. Files, and Julie Weiner

  Background: The mortality of cardiac conditions in infancy is improving with advances in surgical planning and medical management. Neurologic morbidity remains significant, and clinically correlating an infant with their neurologic exam, MRI/EEG, and subsequent developmental testing remains a challenge. Counseling parents regarding neurologic outcomes after cardiac intervention is difficult due to the wide range of findings that can sometimes prove to be clinically irrelevant. Purpose: The goal of this study is to identify factors associated with poor neurodevelopmental outcomes in infants with critical congenital heart defects (CCHD) as assessed by the Bayley Scales of Infant and Toddler Development Edition IV (Bayley). Methods: This is a retrospective single site study performed at a freestanding children’s hospital with delivery services. Neonates were either inborn or admitted to the neonatal or cardiac intensive care units following diagnosis of CCHD over a 5-year period who required cardiac surgical procedures during their initial hospital stay. Patients were sampled from databases in the heart center and the Children’s Hospital Neonatal Consortium. Neonates were stratified by single vs biventricular repair and Norman category of heart defect (A, B, or C). Primary outcomes included neurologic exam, MRI, and EEG at discharge as well as 12- and 24-month Bayleys. Results: 383 neonates were included in analysis. 57.2% were male with an average gestational age of 39 weeks and average birthweight of 3.2kg. The average length of stay was 36 days. Of the entire sample, 36.3% had Bayleys performed at 12 months and 25.8% at 24 months. 38% of the entire sample underwent a single ventricle repair. 39% were classified as Norman A, 41% Norman B, and 19% Norman C. Approximately 40% of Bayleys were abnormal, with highest impairment in gross motor skills and expressive language. Of the 145 infants with EEGs, 17% showed seizures or focal slowing. Of these abnormal EEGs, approximately 45% had an abnormal Bayley. Of the 146 infants with MRIs, 58% showed ischemia, infarct, atrophy, stroke, or hemorrhage. The odds in favor of an abnormal Bayley at 12 months was 3.11 times higher among infants with abnormal MRIs (95% CI 1.22-7.94, d= 0.63). 6.5% had an abnormal neurologic exam, most commonly hypotonia. Of these abnormal neurologic exams, 73% had abnormal 12-month Bayleys and 87.5% had abnormal 24-month Bayleys. Conclusion: Abnormal neurologic exams, MRI, and EEG at discharge can be associated with abnormal Bayleys in childhood. This study helps delineate risk factors in infants with congenital heart defects that could aid in predicting long-term neurodevelopmental outcomes.

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  3D Bioprinting the Tumor Microenvironment for Immunotherapy Development

  Molly Leyda, Tykeem Manor, John Szarejko, Douglas Myers, and John M. Perry

  The tumor microenvironment (TME) is a complex system that plays a crucial role in tumor progression, immune evasion, and therapy resistance. The TME is composed of various cell types, including tumor cells, stromal cells, and immune cells such as macrophages. Macrophages are versatile myeloid cells which can exhibit both pro-tumoral and anti-tumoral functions, depending on their phenotype and the TME context. M1 macrophages have demonstrated promising pro-inflammatory and anti-tumor effects, while tumor associated M2 macrophages (TAMs) play an anti-inflammatory role and promote tumor immune escape. Understanding the complex interactions between TAMs and the TME is, therefore, essential for developing effective anti-cancer immunotherapies. The pre-clinical development of immunotherapies necessitates using both in vitro and in vivo tumor models. Classical 2D in vitro models are relatively fast and inexpensive but lack the spatial complexity and heterogeneity of the TME. In vivo mouse models provide a more physiologically relevant system for evaluating therapies; however, they are time consuming, expensive, and deficient in several immune cell types, so they fail to accurately recreate the TME. 3D bioprinting technology offers a novel approach for creating complex in vitro models of the TME, allowing for the rapid and cost-effective creation of tissue constructs that mimic the composition of native tissues. Our research is focused on using this technology to recreate the TME by incorporating myeloid, stromal, and tumor cells into 3D bioprinted structures. Utilizing these models, we are investigating the cellular interactions which drive the formation of the TME to gain insights into the enigmatic functions of TAMs. Additionally, these models will aid in the development of novel anti-cancer immunotherapies able to evade or repolarize the immunosuppressive TME. Our creation of 3D bioprinted tumor models will facilitate collaborative efforts to screen a wide range of innovative therapies and support translation from bench to bedside

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  Post-Operative Diagnosis of Anomalous Left Coronary Artery From The Right Pulmonary Artery via Transthoracic Echocardiogram

  Lavina Desai, Sanket Shah, Edo Bedzra, and Christopher Mathis

  A term infant female was diagnosed with a ventricular septal defect (VSD) and aortic coarctation. Preoperative echocardiography and computed tomography angiography (CTA) showed a normal right coronary artery origin, but inconclusive left coronary artery (LCA) origin. There was a normal flow profile in the LCA by echocardiography. She underwent repair with extended end-to-end anastomosis and VSD closure during which surgical inspection revealed a usual appearing, retro pulmonary path of the LCA towards the left sinus of Valsalva. Postoperative echocardiogram revealed mild global dysfunction but no regional wall motion abnormalities. Repeat echocardiogram revealed severe dysfunction most prominent in the anterolateral and posterolateral segments from base to apex. There was new, bidirectional flow in the LCA and abnormal diastolic flow in the posterior right pulmonary artery (RPA) raising suspicion for anomalous origin of the LCA from the RPA (ALCARPA). Cardiac catheterization confirmed the diagnosis. Echocardiography plays a vital role in detection of ALCARPA. However, the usual clues of flow reversal in the LCA, abnormal diastolic flow in the pulmonary artery and sequelae of left ventricular ischemia vary with age and pulmonary artery pressure. CTA is valuable in diagnosis but may suffer from improper contrast timing and motion artifact. When the LCA originates from the RPA, the origin appears normal due to its proximity to the left sinus of Valsalva, even by visual inspection. Meticulous coronary imaging and clinical suspicion are required for timely detection. Invasive angiography is the gold standard for diagnosis. There are few cases associating ALCARPA with aortic coarctation. Presence of a coarctation and VSD lead to sufficient pulmonary hypertension for antegrade LCA flow which hinders the preoperative diagnosis. This case is unique because the coronary anatomy was interrogated before surgery, but ALCARPA was not demonstrated due to a low index of suspicion for this rare anatomy and associated pulmonary hypertension. This case highlights the diagnostic challenge of this association of defects and reiterates the importance of definitive coronary imaging preoperatively. Persistent myocardial dysfunction following coarctation and VSD repair should prompt careful evaluation for ALCARPA.

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  Rhabdomyolysis As a cause of PTH independent hypocalcemia in a child with acute influenza infection

  Samhita Bhattarai and Kelsee Halpin

  INTRODUCTION Hypocalcemia is characterized by abnormally low level of calcium in the blood. Normal reference range for calcium for children between 12- 19-year-old is 8.5-10.6 mg/dl . Severe hypocalcemia is considered as serum calcium level of <7 mg>/dl and can present with tetany, seizures, and life-threatening cardiac arrhythmias. Etiology of hypocalcemia varies but hypoparathyroidism, pseudohypoparathyroidism and Vitamin D deficiency are some of the most common causes encountered by pediatrician endocrinologists. Association of rhabdomyolysis with hypocalcemia and elevated PTH is a rare presentation that should be considered, particularly for those children presenting with acute viral illness. We present a rare case of rhabdomyolysis associated with hypocalcemia not related to hypoparathyroidism. CASE A 12-year-old female presented to the emergency department with body ache, decreased oral intake and vomiting. She was found to be influenza positive. Electrolytes showed hypocalcemia (4.8 mg/dl). She subsequently had an undetectable 25-OH vitamin D level (<5 ng>/ml) and elevated iPTH level (609 pg/ml). We discussed the possibility of her etiology of hypocalcemia to be Vitamin D deficiency although her presentation was atypical at an older age with a negative imaging for rickets, hyperphosphatemia (6.0 mg/dl), and normal alkaline phosphatase (334 unit/L). She also did not have any phenotypic features of Albright’s hereditary osteodystrophy and renal function was within normal limits. She was identified to have elevated creatinine kinase (4829 U/L) supporting rhabdomyolysis secondary to acute influenza as a cause of her hypocalcemia. Rhabdomyolysis, a known complication of influenza infection, causes cell membrane destruction which impairs the normal function of Na-K-ATPase channel. This leads to increase in intracellular sodium activating Na/Ca exchanger which in turn causes influx of calcium intracellularly causing hypocalcemia. Additionally, any injury or infection leads to high phosphorus release from cells due to cell lysis. High phosphorus is also caused by reduced oxidative metabolism in muscles impairing phosphate use. This excess of phosphate then combines with calcium and causes calcium-phosphate complex in soft tissues. Hyperphosphatemia also additionally inhibits 1 alpha hydroxylase limiting formation of calcitriol leading to hypocalcemia. CONCLUSION Our patient had severe hypocalcemia due to influenza-related rhabdomyolysis. Rhabdomyolysis is an important consideration as a cause of hypocalcemia in children, especially with acute viral illness. Accordingly, it is also important to obtain serum electrolytes in patients presenting with rhabdomyolysis as hypocalcemia may lead to complications like seizures and cardiac arrhythmia if not appropriately recognized and treated.

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  Children's Mercy: Dedicated to All Children, Everywhere

  Heather Steel, Katie Dayani, Julia McBride, Keri Swaggart, and Kim Weir

  Children’s Mercy Kansas City was founded in 1897 by sisters Drs. Alice Graham and Katharine Richardson. Their primary objective was to create a hospital where the children of Kansas City and surrounding areas could be treated regardless of their religion, race, or ability to pay. By the early 1920’s segregation became a huddle to accomplishing this dream. To circumvent this problem Dr. Katharine Richardson partnered with Dr. John E. Perry and the staff at Wheatley Provident Hospital, the first private Black hospital in Kansas City, MO, to establish the Mercy Model Ward. This ward provided pediatric care for the Black children in Kansas City and was the first of its kind in the nation. Dr. Richardson was fully committed to providing care to all children, everywhere and this model ward provided the means for her to truly realize her goal.