In situ deposition of nanobodies by an engineered commensal microbe promotes survival in a mouse model of enterohemorrhagic E. coli.

Engineered smart microbes that deliver therapeutic payloads are emerging as treatment modalities, particularly for diseases with links to the gastrointestinal tract. Enterohemorrhagic Escherichia coli (EHEC) is a causative agent of potentially lethal hemolytic uremic syndrome. Given concerns that antibiotic treatment increases EHEC production of Shiga toxin (Stx), which is responsible for systemic disease, novel remedies are needed. EHEC encodes a type III secretion system (T3SS) that injects Tir into enterocytes. Tir inserts into the host cell membrane, exposing an extracellular domain that subsequently binds intimin, one of its outer membrane proteins, triggering the formation of attaching and effacing (A/E) lesions that promote EHEC mucosal colonization. Citrobacter rodentium (Cr), a natural A/E mouse pathogen, similarly requires Tir and intimin for its pathogenesis. Mice infected with Cr(ΦStx2dact), a variant lysogenized with an EHEC-derived phage that produces Stx2dact, develop intestinal A/E lesions and toxin-dependent disease. Stx2a is more closely associated with human disease. By developing an efficient approach to seamlessly modify the C. rodentium genome, we generated Cr_Tir-MEHEC(ΦStx2a), a variant that expresses Stx2a and the EHEC extracellular Tir domain. We found that mouse precolonization with HS-PROT3EcT-TD4, a human commensal E. coli strain (E. coli HS) engineered to efficiently secrete an anti-EHEC Tir nanobody, delayed bacterial colonization and improved survival after challenge with Cr_Tir-MEHEC(ΦStx2a). This study suggests that commensal E. coli engineered to deliver payloads that block essential virulence determinants can be developed as a new means to prevent and potentially treat infections including those due to antibiotic resistant microbes.

Serum cytokine panels in pediatric clinical practice.

BACKGROUND: Cytokines are soluble signaling proteins that regulate inflammation and coordinate immune responses. Serum cytokine panels are increasingly used in medical practice, yet our understanding of cytokines as biomarkers for disease remains limited. OBJECTIVE: We sought to analyze real-world single-center use of a multiplexed cytokine panel, correlate its results with diagnosis and severity, and explore its use in pediatric practice. METHODS: A multiplexed cytokine panel, able to return same-day results, was implemented in April 2020 at the Children's Hospital of Philadelphia (Philadelphia, Pa) and its performance was validated for clinical use. Coded patient data were collected using the REDCap database, and correlations between cytokine levels and outcomes of interest were analyzed retrospectively. RESULTS: Cytokine levels correlate with acuity of care, with patients admitted to the pediatric intensive care unit having the highest cytokine values. Patients with familial hemophagocytic lymphohistiocytosis (fHLH) showed prominent peaks in IFN-γ, IL-10, and TNF, whereas patients with sepsis exhibited high IL-6 and IL-8 with relatively modest IFN-γ. Cytokine release syndrome (CRS) after chimeric antigen receptor T-cell therapy often demonstrated pan-panel positivity at peak levels, with a similar pattern as that of fHLH. A ratio of [IFN-γ] + [IL-10]/[IL-6] + [IL-8] levels was able to distinguish fHLH and CRS from severe sepsis. CONCLUSIONS: Cytokine levels correlate with severity of illness and can help differentiate between syndromes that present similarly, including fHLH and CRS compared with sepsis. Cytokine panels can be used as biomarkers to inform diagnosis and management decisions, but significant work remains to dissect complex clinical patterns of disease.

A Comparison of Parent-Reported Severe Autism With Mild/Moderate Autism Among US Children.

OBJECTIVE: An expert commission has proposed the term "profound" autism for children on the spectrum who are minimally verbal or nonverbal and have intellectual disability (ID), behavioral challenges, and co-occurring conditions. It is unknown whether parents' rating of "severe" autism aligns with the definition of "profound" autism. Using the National Survey of Children's Health, we sought to (1) estimate the prevalence of parent-reported severe autism, (2) identify child characteristics that are associated with severe autism, (3) compare health care utilization, and (4) compare caregiver stress and resilience between families of children with severe versus mild/moderate autism. METHODS: Parent responses on the 2018 to 2019 NSCH were used to compare school-age children with parent-reported severe autism and those with mild/moderate autism. Descriptive statistics, χ2 tests, and logistic regression were used for statistical analysis. RESULTS: Among parents of 1,368 US children with autism, 10.1% characterized their child's autism as severe, a prevalence of 1 in 333. Parents of children with severe autism were more likely to report ID (45% vs 12.1%, p < 0.001), language delay (88% vs 58.7%, p < 0.001), and difficulties in dressing and bathing (67% vs 19.2%, p < 0.001). Children with severe autism had more behavioral problems and co-occurring conditions but were no more likely to see specialists or receive autism-specific behavioral therapy. Their caregivers reported more stress and less resilience. CONCLUSION: The characteristics of "profound" autism and parent-reported "severe" autism significantly overlap, allowing the use of the NSCH for studies of this vulnerable population. Children with profound/severe autism could benefit from more behavioral therapy, specialty care, and family support.

Antibiotic resistance trends among Vibrio vulnificus and Vibrio parahaemolyticus isolated from the Chesapeake Bay, Maryland: a longitudinal study.

Antibiotics are often used to treat severe Vibrio infections, with third-generation cephalosporins and tetracyclines combined or fluoroquinolones alone being recommended by the US Centers for Disease Control and Prevention. Increases in antibiotic resistance of both environmental and clinical vibrios are of concern; however, limited longitudinal data have been generated among environmental isolates to inform how resistance patterns may be changing over time. Hence, we evaluated long-term trends in antibiotic resistance of vibrios isolated from Chesapeake Bay waters (Maryland) across two 3-year sampling periods (2009-2012 and 2019-2022). Vibrio parahaemolyticus (n = 134) and Vibrio vulnificus (n = 94) toxR-confirmed isolates were randomly selected from both sampling periods and tested for antimicrobial susceptibility against eight antibiotics using the Kirby-Bauer disk diffusion method. A high percentage (94%-96%) of V. parahaemolyticus isolates from both sampling periods were resistant to ampicillin and only 2%-6% of these isolates expressed intermediate resistance or resistance to third-generation cephalosporins, amikacin, tetracycline, and trimethoprim-sulfamethoxazole. Even lower percentages of resistant V. vulnificus isolates were observed and those were mostly recovered from 2009 to 2012, however, the presence of multiple virulence factors was observed. The frequency of multi-drug resistance was relatively low (6%-8%) but included resistance against antibiotics used to treat severe vibriosis in adults and children. All isolates were susceptible to ciprofloxacin, a fluoroquinolone, indicating its sustained efficacy as a first-line agent in the treatment of severe vibriosis. Overall, our data indicate that antibiotic resistance patterns among V. parahaemolyticus and V. vulnificus recovered from the lower Chesapeake Bay have remained relatively stable since 2009.IMPORTANCEVibrio spp. have historically been susceptible to most clinically relevant antibiotics; however, resistance and intermediate-resistance have been increasingly recorded in both environmental and clinical isolates. Our data showed that while the percentage of multi-drug resistance and resistance to antibiotics was relatively low and stable across time, some Vibrio isolates displayed resistance and intermediate resistance to antibiotics typically used to treat severe vibriosis (e.g., third-generation cephalosporins, tetracyclines, sulfamethoxazole-trimethoprim, and aminoglycosides). Also, given the high case fatality rates observed with Vibrio vulnificus infections, the presence of multiple virulence factors in the tested isolates is concerning. Nevertheless, the continued susceptibility of all tested isolates against ciprofloxacin, a fluoroquinolone, is indicative of its use as an effective first-line treatment of severe Vibrio spp. infections stemming from exposure to Chesapeake Bay waters or contaminated seafood ingestion.

Uncovering the Genetic Etiology of Inherited Bone Marrow Failure Syndromes Using a Custom-Designed Next-Generation Sequencing Panel.

Inherited bone marrow failure syndromes (IBMFS) are a group of heterogeneous disorders that account for ∼30% of pediatric cases of bone marrow failure and are often associated with developmental abnormalities and cancer predisposition. This article reports the laboratory validation and clinical utility of a large-scale, custom-designed next-generation sequencing panel, Children's Hospital of Philadelphia (CHOP) IBMFS panel, for the diagnosis of IBMFS in a cohort of pediatric patients. This panel demonstrated excellent analytic accuracy, with 100% sensitivity, ≥99.99% specificity, and 100% reproducibility on validation samples. In 269 patients with suspected IBMFS, this next-generation sequencing panel was used for identifying single-nucleotide variants, small insertions/deletions, and copy number variations in mosaic or nonmosaic status. Sixty-one pathogenic/likely pathogenic variants (54 single-nucleotide variants/insertions/deletions and 7 copy number variations) and 24 hypomorphic variants were identified, resulting in the molecular diagnosis of IBMFS in 21 cases (7.8%) and exclusion of IBMFS with a diagnosis of a blood disorder in 10 cases (3.7%). Secondary findings, including evidence of early hematologic malignancies and other hereditary cancer-predisposition syndromes, were observed in 9 cases (3.3%). The CHOP IBMFS panel was highly sensitive and specific, with a significant increase in the diagnostic yield of IBMFS. These findings suggest that next-generation sequencing-based panel testing should be a part of routine diagnostics in patients with suspected IBMFS.

Increased incidence of vibriosis in Maryland, U.S.A., 2006-2019.

BACKGROUND: Vibrio spp. naturally occur in warm water with moderate salinity. Infections with non-cholera Vibrio (vibriosis) cause an estimated 80,000 illnesses and 100 fatalities each year in the United States. Climate associated changes to environmental parameters in aquatic ecosystems are largely promoting Vibrio growth, and increased incidence of vibriosis is being reported globally. However, vibriosis trends in the northeastern U.S. (e.g., Maryland) have not been evaluated since 2008. METHODS: Vibriosis case data for Maryland (2006-2019; n = 611) were obtained from the COVIS database. Incidence rates were calculated using U.S. Census Bureau population estimates for Maryland. A logistic regression model, including region, age group, race, gender, occupation, and exposure type, was used to estimate the likelihood of hospitalization. RESULTS: Comparing the 2006-2012 and 2013-2019 periods, there was a 39% (p = 0.01) increase in the average annual incidence rate (per 100,000 population) of vibriosis, with V. vulnificus infections seeing the greatest percentage increase (53%, p = 0.01), followed by V. parahaemolyticus (47%, p = 0.05). The number of hospitalizations increased by 58% (p = 0.01). Since 2010, there were more reported vibriosis cases with a hospital duration ≥10 days. Patients from the upper eastern shore region and those over the age of 65 were more likely (OR = 6.8 and 12.2) to be hospitalized compared to other patients. CONCLUSIONS: Long-term increases in Vibrio infections, notably V. vulnificus wound infections, are occurring in Maryland. This trend, along with increased rates in hospitalizations and average hospital durations, underscore the need to improve public awareness, water monitoring, post-harvest seafood interventions, and environmental forecasting ability.

Depression and anxiety in caregivers of patients with functional seizures.

OBJECTIVE: Contrary to patients, the psychological impact of functional seizures to caregivers has not been adequately investigated. This study aimed to evaluate the rates and determinants of depression and anxiety in caregivers of patients with functional seizures. METHODS: Patients with functional seizures and their caregivers completed surveys about demographic, disease-related, and psychosocial characteristics. Rates and determinants of depression and anxiety were evaluated using the Beck Depression and Anxiety Inventory scores as dependent variables and patient and caregiver characteristics as independent variables. RESULTS: Twenty-nine patients (76% female, mean age of 37 years) and their caregivers (59% female, mean age of 43 years) were recruited. Symptoms of anxiety and/or depression were present in 96% of patients (96% depression, 92% anxiety) and 59% of caregivers (52% depression, 50% anxiety). Specifically, 31% of caregivers manifested mild depression, 14% moderate depression, and 7% severe depression, whereas 48% were not depressed. Similarly, 14% of caregivers manifested mild anxiety, 29% moderate anxiety, and 7% severe anxiety, whereas 50% were not anxious. Patient and caregiver depression levels strongly correlated (r = .73, p < .0001). The presence of anxiety and depression in the caregiver was associated with male patient gender (p = .02), patient depression level (p = .002), the caregiver being a parent or sibling (p = .02), and caregiver burden (p = .0009). SIGNIFICANCE: Caregivers of patients with functional seizures experience high rates of anxiety and depression, explained by specific demographic and psychosocial factors that could act as intervention targets.

A global call for action to tackle skin-related neglected tropical diseases (skin NTDs) through integration: An ambitious step change.

On 8 June 2022, the World Health Organization (WHO) released pivotal guidance, "Ending the neglect to attain the Sustainable Development Goals: A strategic framework for integrated control and management of skin-related neglected tropical diseases." Skin-related neglected tropical diseases, or skin NTDs, comprise a group of NTDs that produce signs and symptoms on the skin and include at least 9 diseases or disease groups. Moving away from disease-specific approaches, it is anticipated that synergies will be identified and integrated building on this shared feature, where possible, to achieve a greater health impact. This paper intends to draw attention to the prospects created by this scheme. The framework is a key basis for a proposal produced by WHO dedicated to skin NTD integration and describes the practical opportunities for this evolving strategy. It underlines the wider health benefits that will follow, thus working towards Universal Health Coverage and skin health for all.

Opportunities to improve high-risk behavior screenings during well-child examinations.

BACKGROUND: Nurse practitioners serve an essential role in the completion of age-appropriate adolescent high-risk behavior screenings including tobacco/nicotine, alcohol, illicit drug use, and sexual activity during well-child examinations (WCEs). LOCAL PROBLEM: Midwestern adolescents demonstrate a suboptimal rate of engaging in annual preventative medical visits in comparison to national data. METHODS: This mixed-methods quality improvement pilot sought to evaluate health care providers' beliefs, general clinic processes, and the overall quality of WCEs among adolescents aged 11-17 years in two midwestern primary care clinics. Quantitative data were obtained through queried reports and manual electronic health record chart audits. Qualitative data were obtained through focus group interviews. INTERVENTIONS: Interventional strategies included providing education to key stakeholders regarding data analysis findings indicating process deficiencies regarding adolescent WCEs. Project members championed integration of advanced practice nurses as leaders of change within urban, multisite tertiary health care systems. RESULTS: Results demonstrate that the lack of standardized assessment during an adolescent WCE can lead to fragmentation of high-risk behavior screenings. CONCLUSIONS: This quality improvement pilot demonstrates the need for nurse practitioners to be at the forefront of interprofessional committees advancing the implementation of evidence-based guidelines and practice improvement initiatives. Standardization of high-risk behavior screening as part of the WCE in adolescence provides the foundation for health promotion and chronic disease prevention spanning into adulthood.

Effects of Calcium and Phosphate on Dissolution of Enamel, Dentin and Hydroxyapatite in Citric Acid.

The aim was to evaluate the effect of dissolved calcium and phosphate on dissolution rate of enamel, dentin and compressed hydroxyapatite (HA) in citric acid solution as a function of pH. At pH 2.5, dissolution rate of enamel increased significantly by 6% in 20 mmol/L added calcium but, otherwise, dissolution rates of neither enamel, dentin nor HA were significantly affected by 10 or 20 mmol/L calcium. However, enamel dissolution rate was reduced by > 50 mmol/L calcium. At pH 3.25 and 4.0, 10-20 mmol/L calcium inhibited dissolution of enamel by 29-100% and HA by 65-75% but did not affect dentin dissolution. Phosphate (10 or 20 mmol/L) did not inhibit dissolution of enamel, dentin or HA at any pH, but there were increases in dissolution rate of all three substrates at pH 2.5 and, in one test with dentine (at 20 mmol/L phosphate), at pH 3.25. The results suggest that calcium addition to soft drinks and other acidic products such as medications may reduce erosivity against enamel, provided that pH is not too low; that phosphate would not reduce erosivity against enamel; and that neither calcium nor phosphate at these concentrations would reduce erosivity against dentin.

Constructing a polygenic risk score for childhood obesity using functional data analysis.

Obesity is a highly heritable condition that affects increasing numbers of adults and, concerningly, of children. However, only a small fraction of its heritability has been attributed to specific genetic variants. These variants are traditionally ascertained from genome-wide association studies (GWAS), which utilize samples with tens or hundreds of thousands of individuals for whom a single summary measurement (e.g., BMI) is collected. An alternative approach is to focus on a smaller, more deeply characterized sample in conjunction with advanced statistical models that leverage longitudinal phenotypes. Novel functional data analysis (FDA) techniques are used to capitalize on longitudinal growth information from a cohort of children between birth and three years of age. In an ultra-high dimensional setting, hundreds of thousands of single nucleotide polymorphisms (SNPs) are screened, and selected SNPs are used to construct two polygenic risk scores (PRS) for childhood obesity using a weighting approach that incorporates the dynamic and joint nature of SNP effects. These scores are significantly higher in children with (vs. without) rapid infant weight gain-a predictor of obesity later in life. Using two independent cohorts, it is shown that the genetic variants identified in very young children are also informative in older children and in adults, consistent with early childhood obesity being predictive of obesity later in life. In contrast, PRSs based on SNPs identified by adult obesity GWAS are not predictive of weight gain in the cohort of young children. This provides an example of a successful application of FDA to GWAS. This application is complemented with simulations establishing that a deeply characterized sample can be just as, if not more, effective than a comparable study with a cross-sectional response. Overall, it is demonstrated that a deep, statistically sophisticated characterization of a longitudinal phenotype can provide increased statistical power to studies with relatively small sample sizes; and shows how FDA approaches can be used as an alternative to the traditional GWAS.

Resource dilution in maternal feeding practices after birth of a secondborn.

Firstborn children have higher prevalence of obesity than secondborn siblings. The birth of a sibling typically results in resource dilution when mothers begin to divide their time and attention between two children. This mixed-methods analysis applies the family systems process of resource dilution to test the hypothesis that characteristics of the secondborn impact how parents feed the firstborn. Participants (n = 76) were mothers of consecutively born firstborn and secondborn siblings who participated in the INSIGHT trial and an observational cohort. Quantitative analyses involved multilevel models to test if characteristics of secondborns (temperament at 16 weeks, appetite at 28 weeks) were associated with maternal feeding practices of firstborns (structure and control-based feeding) at 1, 2, and 3 years, adjusting for firstborn child characteristics. A purposive subsample (n = 30) of mothers participated in semi-structured interviews to contextualize potential sibling influences on maternal feeding practices during infancy and toddlerhood. Quantitative data showed secondborn temperament and appetite were associated with how mothers fed their firstborn. Qualitative data explained maternal feeding practices in three primary ways: 1) Mothers explained shifting predictable meal and snack routines after birth of the secondborn, but did not perceive sibling characteristics as the source; 2) Family chaos following the secondborn's birth led to "survival mode" in feeding; and 3) Social support was protective against feeding resource dilution. The family systems process of resource dilution is a focus for future research and support for families during key transitions and a direction for efforts to reduce risk for child obesity.

Sharp decline in rates of community respiratory viral detection among patients at the National Institutes of Health Clinical Center during the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVES: To analyze the frequency and rates of community respiratory virus infections detected in patients at the National Institutes of Health Clinical Center (NIHCC) between January 2015 and March 2021, comparing the trends before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted a retrospective study comparing frequency and rates of community respiratory viruses detected in NIHCC patients between January 2015 and March 2021. Test results from nasopharyngeal swabs and washes, bronchoalveolar lavages, and bronchial washes were included in this study. Results from viral-challenge studies and repeated positives were excluded. A quantitative data analysis was completed using cross tabulations. Comparisons were performed using mixed models, applying the Dunnett correction for multiplicity. RESULTS: Frequency of all respiratory pathogens declined from an annual range of 0.88%-1.97% between January 2015 and March 2020 to 0.29% between April 2020 and March 2021. Individual viral pathogens declined sharply in frequency during the same period, with no cases of influenza A/B orparainfluenza and 1 case of respiratory syncytial virus (RSV). Rhino/enterovirusdetection continued, but with a substantially lower frequency of 4.27% between April 2020 and March 2021, compared with an annual range of 8.65%-18.28% between January 2015 and March 2020. CONCLUSIONS: The decrease in viral respiratory infections detected in NIHCC patients during the pandemic was likely due to the layered COVID-19 prevention and mitigation measures implemented in the community and the hospital. Hospitals should consider continuing the use of nonpharmaceutical interventions in the future to prevent nosocomial transmission of respiratory viruses during times of high community viral load.

Case study of invalid to valid shift in cognitive performance following successful treatment of psychogenic nonepileptic seizure events.

Patients with psychogenic nonepileptic seizure (PNES) who fail performance validity testing (PVT) may appear to produce non-valid cognitive profiles. Consequently, they may not get referred to treatment and events persist, with worsening disability and high resource utilization. As a result, we report pre- and post-treatment neuropsychological evaluation findings in a 59-year-old woman with a confirmed diagnosis of PNES established using video-EEG monitoring. At pre-treatment baseline neuropsychological evaluation, PNES events occurred weekly to daily. Performance was impaired across PVTs and across multiple cognitive domains. After behavioral intervention specific to PNES, these events substantially reduced in frequency to rare stress-induced flares. Post-treatment neuropsychological evaluation revealed marked improvement of most cognitive and behavioral scores from baseline, and valid PVT scores. We review predisposing, precipitating, and perpetuating factors for PNES and cognitive impairment in this case and discuss the patient's outcome from treatment. Effectively managing PNES events and dissociative tendencies while reducing unnecessary pharmacological interventions appears to have allowed this patient to function closer to her optimal state. This case illustrates the complexity of Functional Neurologic Disorder (FND) clinical presentation and challenges the assumption that suboptimal neuropsychological performance predicts poor treatment engagement and outcome. We showcase the reversibility of PNES and cognitive manifestations of FND using targeted psychotherapeutic interventions, which resulted in reduced disability and associated healthcare costs, as well as re-engagement in life.

A solution to the challenges of interdisciplinary aggregation and use of specimen-level trait data.

Understanding variation of traits within and among species through time and across space is central to many questions in biology. Many resources assemble species-level trait data, but the data and metadata underlying those trait measurements are often not reported. Here, we introduce FuTRES (Functional Trait Resource for Environmental Studies; pronounced few-tress), an online datastore and community resource for individual-level trait reporting that utilizes a semantic framework. FuTRES already stores millions of trait measurements for paleobiological, zooarchaeological, and modern specimens, with a current focus on mammals. We compare dynamically derived extant mammal species' body size measurements in FuTRES with summary values from other compilations, highlighting potential issues with simply reporting a single mean estimate. We then show that individual-level data improve estimates of body mass-including uncertainty-for zooarchaeological specimens. FuTRES facilitates trait data integration and discoverability, accelerating new research agendas, especially scaling from intra- to interspecific trait variability.

Genetic modifications designed for xenotransplantation attenuate sialoadhesin-dependent binding of human erythrocytes to porcine macrophages.

The phenomenon of diminishing hematocrit after in vivo liver and lung xenotransplantation and during ex vivo liver xenoperfusion has largely been attributed to action by resident liver porcine macrophages, which bind and destroy human erythrocytes. Porcine sialoadhesin (siglec-1) was implicated previously in this interaction. This study examines the effect of porcine genetic modifications, including knockout of the CMAH gene responsible for expression of Neu5Gc sialic acid, on the adhesion of human red blood cells (RBCs) to porcine macrophages. Wild-type (WT) porcine macrophages and macrophages from several strains of genetically engineered pigs, including CMAH gene knockout and several human transgenes (TKO+hTg), were incubated with human RBCs and "rosettes" (≥3 erythrocytes bound to one macrophage) were quantified by microscopy. Our results show that TKO+hTg genetic modifications significantly reduced rosette formation. The monoclonal antibody 1F1, which blocks porcine sialoadhesin, significantly reduced rosette formation by WT and TKO+hTg macrophages compared with an isotype control antibody. Further, desialation of human RBCs with neuraminidase before addition to WT or TKO+hTg macrophages resulted in near-complete abrogation of rosette formation, to a level not significantly different from porcine RBC rosette formation on porcine macrophages. These observations are consistent with rosette formation being mediated by binding of sialic acid on human RBCs to sialoadhesin on porcine macrophages. In conclusion, the data predict that TKO+hTg genetic modifications, coupled with targeting of porcine sialoadhesin by the 1F1 mAb, will attenuate erythrocyte sequestration and anemia during ex vivo xenoperfusion and following in vivo liver, lung, and potentially other organ xenotransplantation.

Non-myeloablative conditioning is sufficient to achieve complete donor myeloid chimerism following matched sibling donor bone marrow transplant for myeloproliferative leukemia virus oncogene (MPL) mutation-driven congenital amegakaryocytic thrombocytopenia: Case report.

Background: Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare platelet production disorder caused mainly by loss of function biallelic mutations in myeloproliferative leukemia virus oncogene (MPL), the gene encoding the thrombopoietin receptor (TPOR). Patients with MPL-mutant CAMT are not only at risk for life-threatening bleeding events, but many affected individuals will also ultimately develop bone marrow aplasia owing to the absence of thrombopoietin/TPOR signaling required for maintenance of hematopoietic stem cells. Curative allogeneic stem cell transplant for patients with CAMT has historically used myeloablative conditioning; however, given the inherent stem cell defect in MPL-mutant CAMT, a less intensive regimen may prove equally effective with reduced morbidity, particularly in patients with evolving aplasia. Methods: We report the case of a 2-year-old boy with MPL-mutant CAMT and bone marrow hypocellularity who underwent matched sibling donor bone marrow transplant (MSD-BMT) using a non-myeloablative regimen consisting of fludarabine, cyclophosphamide, and antithymocyte globulin (ATG). Results: The patient achieved rapid trilinear engraftment and resolution of thrombocytopenia. While initial myeloid donor chimerism was mixed (88% donor), due to the competitive advantage of donor hematopoietic cells, myeloid chimerism increased to 100% by 4 months post-transplant. Donor chimerism and blood counts remained stable through 1-year post-transplant. Conclusion: This experience suggests that non-myeloablative conditioning is a suitable approach for patients with MPL-mutant CAMT undergoing MSD-BMT and is associated with reduced risks of conditioning-related toxicity compared to traditional myeloablative regimens.