United States

Abstract Title
Improving Access and Outcomes: A Comprehensive Look at Breast Cancer Care in Ghana
Background
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related mortality among Ghanaian women, accounting for nearly one-third of new cancer cases in 2020. Diagnosis typically occurs around age 49, with nearly half of patients presenting at advanced stages. Although cancer services have expanded, access to early detection and follow-up care continues to vary based on geography and socioeconomic status. This review examines national trends in breast cancer screening, treatment availability, and survivorship, with a focus on actionable strategies to improve access and outcomes.
Methods
We conducted a comprehensive review of peer-reviewed literature, national datasets, and clinical trial registries, including analysis of the 2022 Ghana Demographic and Health Survey. To evaluate how access to screening varied across sociodemographic groups, we used chi-square tests and built a multivariable logistic regression model to calculate adjusted odds ratios (ORs) for breast cancer screening by wealth quintile, education level, and residence.
Results
Survey data suggest that fewer than one in five women aged 15–49 in Ghana have ever received a breast cancer screening. Screening rates were significantly higher among women with greater wealth, education, and those living in urban areas (p &lt; 0.0001 for all comparisons). Women in the highest wealth quintile had over six times the odds of screening compared to those in the lowest (OR 6.11; 95% CI: 5.18–7.20). Education had an even stronger association, with women who had more than secondary schooling nearly nine times more likely to be screened than those with no formal education (OR 8.98; 95% CI: 7.57–10.66). Urban residence was associated with twice the odds of screening compared to rural residence (OR 2.13; 95% CI: 1.95–2.33).
Patterns of inequity are also mirrored in the distribution of treatment services. For instance, chemotherapy and radiation remain primarily available in Accra, Kumasi, and Tamale. Services essential for survivorship, including surveillance imaging and psychosocial support, also remain concentrated at major referral hospitals.
Conclusion
These findings highlight persistent differences in breast cancer screening and treatment access across wealth, education, and geography, and emphasize the need for targeted improvements to reach underserved populations. Addressing these issues through data-driven planning, patient-centered education, and coordinated service delivery can lead to more equitable care and earlier detection. This work offers a meaningful contribution to breast cancer research in Ghana and informs future strategies for improving access, reducing delays, and supporting patients across all stages of care.

AMA Research Challenge 2025 

Improving Access and Outcomes: A Comprehensive Look at Breast Cancer in Ghana

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AMA Research Challenge 2023

Join the AMA Research Challenge poster symposium and semifinals to explore top research posters, score posters in the semifinals (an AMA member exclusive opportunity) and attend education sessions with experienced physicians to learn tips to advance your research and career. 

Abstract Title
Improving Access and Outcomes: A Comprehensive Look at Breast Cancer Care in Ghana
Background
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related mortality among Ghanaian women, accounting for nearly one-third of new cancer cases in 2020. Diagnosis typically occurs around age 49, with nearly half of patients presenting at advanced stages. Although cancer services have expanded, access to early detection and follow-up care continues to vary based on geography and socioeconomic status. This review examines national trends in breast cancer screening, treatment availability, and survivorship, with a focus on actionable strategies to improve access and outcomes.
Methods
We conducted a comprehensive review of peer-reviewed literature, national datasets, and clinical trial registries, including analysis of the 2022 Ghana Demographic and Health Survey. To evaluate how access to screening varied across sociodemographic groups, we used chi-square tests and built a multivariable logistic regression model to calculate adjusted odds ratios (ORs) for breast cancer screening by wealth quintile, education level, and residence.
Results
Survey data suggest that fewer than one in five women aged 15–49 in Ghana have ever received a breast cancer screening. Screening rates were significantly higher among women with greater wealth, education, and those living in urban areas (p < 0.0001 for all comparisons). Women in the highest wealth quintile had over six times the odds of screening compared to those in the lowest (OR 6.11; 95% CI: 5.18–7.20). Education had an even stronger association, with women who had more than secondary schooling nearly nine times more likely to be screened than those with no formal education (OR 8.98; 95% CI: 7.57–10.66). Urban residence was associated with twice the odds of screening compared to rural residence (OR 2.13; 95% CI: 1.95–2.33).
Patterns of inequity are also mirrored in the distribution of treatment services. For instance, chemotherapy and radiation remain primarily available in Accra, Kumasi, and Tamale. Services essential for survivorship, including surveillance imaging and psychosocial support, also remain concentrated at major referral hospitals.
Conclusion
These findings highlight persistent differences in breast cancer screening and treatment access across wealth, education, and geography, and emphasize the need for targeted improvements to reach underserved populations. Addressing these issues through data-driven planning, patient-centered education, and coordinated service delivery can lead to more equitable care and earlier detection. This work offers a meaningful contribution to breast cancer research in Ghana and informs future strategies for improving access, reducing delays, and supporting patients across all stages of care.

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Background
The viability of a transplanted organ and the patient’s health are inherently limited by the burdens of immunosuppressive therapy, which must be used for the duration of the patient’s life. Systemic administration of these immunosuppressive agents increases the incidence of infectious disease and malignancy, which are the leading causes of death in transplant patients. New tolerance induction strategies are limited by technical difficulties to only be used for living donor transplants. Developments in ex vivo machine perfusion of transplanted organs offer a unique therapeutic opportunity to treat donor organs prior to their implantation into the recipient. I designed a novel targeting system that leverages advances in ex vivo perfusion to implant a bio-orthogonal surface targeting moiety (i.e., a receiving peptide) on an organ, which is introduced to the organ via ex vivo perfusion during its time in transport. This targeting system will allow for the systemic dosing of lipid nanoparticles (LNPs), carrying nucleic acid therapeutics to traffic only to the transplanted organ via a docking peptide, creating a platform for targeted drug delivery that minimizes off-target side effects and maximizes the efficacy of long-term therapeutic treatment. 

Methods
A unique orthogonal protein receptor was designed and cloned into a lentiviral backbone. This was used to engineer a cell line that permanently expressed the orthogonal receptor. GFP mRNA was generated via in vitro transcription and encapsulated in LNPs. Targeting peptides were chemically conjugated to the PEG component of the formulation and were added to the LNPs using a post-insertion technique. Engineered cells were treated with high and low doses of LNPs for 20 minutes on an orbital shaker, after which the LNP treatment condition was removed and replaced with fresh media.

Results 
The orthogonal cell line demonstrated significantly better uptake of the cell targeting LNPs. Receptor expression (visualized via mCherry) correlated with increased GFP cargo expression, demonstrating the targeting capabilities of the system.

Conclusion 
We achieved a successful proof of concept, not only that orthogonal targeting was possible, but also demonstrated that it occurs rapidly under non-static conditions. This novel targeting technology also has the potential to significantly decrease the dose of nucleic acid therapeutic required for efficacy. Implementation of BIONATS is now occurring in primary endothelial cells, with future plans to begin testing in ex vivo perfusion systems and demonstrate organ localization in a murine orthotopic heart transplant model.


A Bio-Orthogonal Targeting System for Precision Drug Delivery to Transplanted Hearts

Background
Optimal blood pressure (BP) management during mechanical thrombectomy (MT) for acute stroke is critical for improving outcomes. Current guidelines recommend maintaining systolic BP (SBP) between 140-180 mm Hg, diastolic BP (DBP) below 105 mm Hg, and Mean Arterial Pressure (MAP) above 70 mm Hg, but provide no guidance as to whether invasive or noninvasive monitoring is preferred. Implementing best practices for BP monitoring could significantly enhance care in this high-risk patient population.


Methods
We conducted a retrospective review of 133 electronic medical records of patients undergoing MT for acute stroke at our institution between August 2023 and October 2024. We compared time spent within recommended BP targets and vasoactive medication use between cases monitored with arterial lines (a-line group) and those using noninvasive (NIBP) monitoring. 


Results
A-lines were used in over 88% of MT cases. SBP deviated from the recommended range (140-180 mm Hg) in 56.6 ± 14.2 % of NIBP cases and 49.0 ± 14.6 % of a-line cases (P = 0.034). Hypotension (SBP <140 mm Hg) was common across all cases. The use of phenylephrine boluses was significantly higher in the NIBP group compared to the a-line group (P=0.008). 


Conclusion
While a-line monitoring was associated with better BP control during MT, deviations below the recommended BP ranges were frequent, regardless of the choice of BP monitoring method. These findings underscore the need for enhanced institutional education and adherence to BP management protocols in this high-risk patient population.

Anesthesia Practices Surrounding Emergent Mechanical Thrombectomy for Acute Strokes: A Single Center Experience

Background: The gut microbiome plays a vital role in influencing cancer prognosis by
regulating immune responses and chemotherapy tolerance. While this relationship is well-studied in colorectal and other cancers, research in breast cancer remains limited. Identifying associations between microbiome diversity and host demographic and clinical prognostic factors may uncover novel predictive markers and inform precision oncology strategies. This study investigates the relationship between microbial diversity, measured at different treatment stages, and demographic and clinical variables in newly diagnosed Black and White breast cancer patients.

Methods: This is a prospective, ongoing gut microbiome study of 59 newly diagnosed breast cancer patients (Black = 28, White = 29, Other = 2) enrolled at Moffitt Cancer Center. Stool samples were collected at different treatment stages, with 47 women providing ≥1 stool sample thus far. At-home collections were conducted using a previously validated kit optimized for this
patient population. Alpha (observed species/genes and the Shannon index for species/genes) were calculated from the rarefied filtered species table. Other key factors, including age, race, BMI, education level, menopausal status, tumor stage, breast cancer subtype, were collected through chart abstraction and questionnaire. Flow cytometry was used to identify immune markers (e.g., CD4, CD8, PD-L1) within blood samples. Descriptive statistics were used to summarize participant characteristics. Associations between microbial diversity and demographic factors will be analyzed using non-parametric tests.

Results: Among 59 participants (mean age 55 years; mean BMI 31.4 kg/m²), the majority were Black (47%) or White (49%). At the patient level, we observed that the microbial diversity was similar between Black (3.53, 0.67) and White (3.52, 0.72) patients (median Shannon index, IQR). Participants >50 years showed higher diversity (3.52, 0.70) than those ≤50 (3.10, 1.01). Diversity increased with BMI, peaking in patients with BMI >29.9 (3.52, 0.68). Stage III cancers had the highest diversity (median =3.59), and HER2-enriched tumors showed the highest median Shannon index (median =3.87) among molecular subtypes. Analyses were conducted in Microsoft Excel; future work will use R and SAS for more robust statistical testing and incorporate immune makers.

Conclusion: These preliminary findings suggest that gut microbial diversity may vary with key host and tumor characteristics, underscoring its potential as a biomarker for prognosis and therapeutic response in breast cancer. Continued investigation into these associations could inform future precision oncology strategies and support the integration of microbiome metrics into individualized cancer care.

Gut Microbiome Diversity and Its Associations with Demographic and Clinical Prognostic Characteristics in Breast Cancer Patients

Background
Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications, primarily used for treatment of peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), and dyspepsia. By irreversibly inhibiting the hydrogen potassium ATPase pump in gastric parietal cells, PPIs help reduce gastric acid secretion, providing effective relief from symptoms such as acid reflux, epigastric pain, and heartburn. Although PPIs are generally considered safe for short-term use, emerging literature has suggested a variable, yet up-trending association between PPI use and an increased risk of acute kidney injury (AKI), especially within inpatient hospital settings. However, a clear quantification of this increased risk remains unclear. This meta-analysis aims to further evaluate and quantify the risk of postoperative AKI associated with perioperative prophylactic PPI usage.

Methods
To identify relevant studies, we conducted a focused database search using Google Scholar, ScienceDirect, and PubMed, particularly focusing on articles published within the last decade. Criteria for study inclusion and exclusion along with search methods deployed were conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. The analysis included 8 studies (N=632,226), comprising retrospective, cohort, and observational studies across diverse surgical populations.

Results
Using a fixed-effect based model, the pooled odds ratio (OR) for AKI events associated with prophylactic PPI use was 1.58 (95% CI: 1.56–1.61), indicating a significant increased risk. In highlight, subgroup analyses demonstrated variability with cardiac surgery populations (OR: 1.21, 95% CI: 1.03–1.42; OR: 2.238, 95% CI: 1.387–3.61) and cancer-related procedures (OR: 1.73, 95% CI: 1.08–2.75) showing pronounced risk.

Conclusion
The findings of this meta-analysis demonstrated a clinically significant increase of AKI incidences with the involvement of prophylactic PPI across various perioperative surgical inpatient settings. Given the strength of the pooled results, clinicians should carefully take into consideration the anticipated risk and benefits of prescribing PPIs within the course of patients undergoing major surgeries or operations, especially regarding renal harm and outcome. Future studies should further evaluate the underlying mechanisms behind this delicate relationship alongside exploring insights in optimal strategies in minimizing AKI damage from PPI usage.


Proton Pump Inhibitor Effects on Postoperative Acute Kidney Injury: A Meta-Analysis

Background
FOXG1 syndrome (OMIM 613454) is a rare disease that is classified as a high-confidence syndromic cause of autism spectrum disorder (ASD). The predicted incidence of FOXG1 syndrome is 2.8-3.5 per 100,000 live births, and approximately 1200 individuals have been identified with FOXG1 syndrome. The symptoms of FOXG1 syndrome encompass many organ systems and include examples such as developmental delay, intellectual disability, microcephaly, epilepsy, movement disorders, hypotonia, and feeding and gastrointestinal difficulties. Missense, nonsense, deletion, frameshift, and duplication variants in the FOXG1 gene have been classified as pathogenic, and most of those variants are de novo. Our understanding of how genetic variants in FOXG1 lead to the diverse range of clinical symptoms observed in affected individuals remains limited, and there are currently no targeted treatments available for FOXG1 syndrome. Therefore, this study aims to uncover genotype-phenotype relationships, identify plasma biomarkers, and determine whether patient-specific variant mouse model phenotypes are reflective of patient phenotypes.

Methods
Using the innovative Citizen Health platform and the FOXG1 Research Foundation Patient Registry, we have collected medical records and caregiver-reported patient data. Additionally, we have conducted plasma proteomics studies for 12 patients with FOXG1 syndrome and 126 age-matched control samples to identify possible biomarkers. We have also developed and characterized four patient-specific variant mouse models, Foxg1 c.250dupC (p.Q84Pfs*31), c.483del (p.G161Gfs*23), c.646G>A (p.G216S), and c.900G>A (p.W300X). 

Results
Genetic analysis of the FOXG1 Research Foundation Patient Registry and Citizen Health data demonstrated a diverse spectrum of genetic variants and phenotypes among the affected individuals with confirmed pathogenic variants in FOXG1. Moreover, we have discovered numerous differentially expressed proteins from our proteomics analysis, with several key pathways and processes being disrupted in FOXG1 syndrome patients, including chromatin remodeling and neuroimmune activation. In our patient-specific variant mouse models, we have identified anatomical brain deficits, motor deficits, impaired communication, impaired hippocampal-dependent learning, and social cognition deficits; thus, these models exhibit overlap with FOXG1 syndrome patient phenotypes.

Conclusion
We assembled a large FOXG1 syndrome patient cohort to perform molecular characterization of FOXG1 variants and assess phenotypic impacts. We also identified potential plasma biomarkers using proteomics and developed patient-specific mouse models that recapitulate patient phenotypes. Together, these efforts advance our understanding of the pathophysiology of FOXG1 syndrome and support the future development of targeted therapeutic strategies.

Genotype-Phenotype Mapping, Biomarker Discovery, and Modeling of FOXG1 Syndrome

Background
Pediatric patients with autonomic disorders often experience disabling symptoms such as fatigue, dizziness, abdominal pain, and syncope that limit daily functioning. The Functional Disability Inventory (FDI) is commonly used to assess disability in children and adolescents, with both self- and parent-report forms available. While prior studies show that children often report higher disability levels than their parents, little is known about the concordance of FDI scores in the context of autonomic disorders and symptom subtypes.

Methods
This study assessed FDI scores from both pediatric patients and their caregivers at a autonomic disorder clinic. Additional symptom-based surveys were administered, including fatigue assessments, orthostatic intolerance profiles, and gastrointestinal symptom checklists, to explore correlations between symptom domains and disability perception. FDI sum scores from child and parent surveys were calculated and compared using paired t-tests. Pearson correlation coefficients were used to evaluate agreement between parent- and child-reported FDI scores. Subgroup analyses assessed whether specific symptoms were associated with greater parent-child scoring discrepancies.

Results
A strong positive correlation was observed between child and parent FDI scores, suggesting that caregiver reports can serve as reliable proxies when child self-report is unavailable. Fatigue emerged as the strongest predictor of perceived disability across both respondent groups. On average, parents reported slightly higher levels of disability than their children, though the mean difference in FDI scores (–1.49) was not statistically significant (p = 0.1353). No substantial variation in FDI concordance was found across different autonomic diagnoses.

Conclusion
Caregiver-reported FDI scores are closely aligned with child self-reports in pediatric patients with autonomic disorders, particularly when fatigue is a prominent symptom. These findings support the clinical use of parent reports as a valid substitute for self-reports in the functional assessment of pediatric autonomic patients. Future research should investigate longitudinal changes in FDI scores to track evolving perceptions of disability and treatment response.

Concordance in FDI Scores Between Pediatric Autonomic Patients and Their Caregivers

Background
Breastfeeding (BF) is widely encouraged for maternal and infant health. Early cessation is frequently associated with postpartum depression (PPD). Difficulty with BF and low self-efficacy may contribute to depressive symptoms, creating a bidirectional relationship between BF challenges and PPD. International Board Certified Lactation Consultants (IBCLCs) have been shown to improve BF duration and maternal mental health through support and education. We hypothesized that postpartum patients with elevated depressive symptoms (PHQ-9 ≥5) would experience a significant reduction in depressive symptoms following consultation with an IBCLC. This study aimed to evaluate the relationship between IBCLC consultation and changes in PHQ-9 scores in this population.
Methods
Retrospective cohort analysis was conducted with 34 patients. Paired t-tests assessed pre- and post-consultation PHQ-9 score changes among patients with baseline scores ≥5.
Results
Among 34 patients with PHQ-9 ≥5, mean scores decreased significantly from 7.71 ± 2.50 to 4.18 ± 3.07 after IBCLC intervention (t(33) = 4.88, p < 0.0001).
Conclusion
Postpartum patients with elevated depressive symptoms experienced a significant reduction in PHQ-9 scores following IBCLC consultation. These findings support the potential role of lactation support as a non-pharmacologic intervention for improving emotional wellbeing in at-risk postpartum individuals. Further studies with larger sample sizes and standardized timing are warranted to validate these results.

Impact of Lactation Consultation on PHQ-9 Scores Among Postpartum Individuals with Elevated Baseline Depressive Symptoms: A Retrospective Cohort Analysis from a Midwestern Health System

Background:
Cutaneous malignancies pose a significant burden to public health, with prevention
being critical for improving health outcomes. This study analyzed the demographic and clinical characteristics of 435 uninsured patients presenting to an outpatient, low-income, community dermatology clinic. The goal was to assess the incidence of
cutaneous neoplasms and pre-cancer lesions and identify disparities in preventive care.

Methods:
We retrospectively analyzed 435 electronic medical records collected from an
outpatient, predominantly low-income, community dermatology clinic from 2021 to 2024. Diagnoses and management plans were made by board-certified dermatologists or resident physicians under dermatologist supervision. Data on race, ethnicity, sex, age, diagnoses and treatment plans were extracted for analysis.

Results:
Demographic data were collected, among 435 patients, yielding: Race: White (n=230), Black (n=87), Asian/Pacific Islander (n=24), Hispanic (n=12), Prefer not to answer (n=82). Ethnicity: Hispanic or Latino (n=95), Not Hispanic or Latino (n=294), Unknown (n=34), Prefer not to answer (n=12). Gender: Male (n=160), Female (n=275). The mean age was 50.8 (SD 12.4). Our data reveal a total of 86 (20%) patients diagnosed with cutaneous neoplasms or pre-cancerous lesions. Actinic keratoses were diagnosed in 38 (9%) patients, basal cell carcinomas in 29 (6%), squamous cell carcinomas in 15 (3%), and melanoma in 4 (1%). A total of three patients were using chemoprevention, with 2 (0.5%) using 5-fluorouracil and 1 (0.2%) using acitretin.

Discussion:
Our data underscores the high prevalence of pre-cancerous and cancerous lesions in low-income communities, but the underutilization of therapies that could mitigate
disease progression. Notably, 20% of patients were diagnosed with a pre-cancerous or cancerous lesion, but less than 1% of patients were receiving chemo-preventative care.

Conclusion:
Cutaneous neoplasms and pre-cancerous lesions were noted at a considerably high
incidence in our free clinic population. However, chemo-prevention was relatively low compared to the diagnosed cancers and pre-cancers. Further research should evaluate the perceptions and barriers for chemoprevention among low-income populations at risk of skin cancer.

Cutaneous Malignancies and Chemoprevention in Underserved Communities: A Retrospective Analysis

Background
Ehlers-Danlos Syndrome (EDS) is a group of connective tissue disorders often associated with hyperflexibility, dysautonomia, and gastrointestinal (GI) dysmotility. Although gastroparesis related to EDS is often underrecognized, it can lead to significant morbidity and impacts on quality of life when refractory to many medical therapies. We present a case of medically refractory gastroparesis in a young female patient with hypermobile EDS (hEDS; EDS Type 3), gastroparesis, sick sinus syndrome (SSS), and postural orthostatic hypotension (POTS) who experienced clinical improvement following gastric per-oral endoscopic myotomy (G-POEM).
Case Presentation
A 23-year-old woman with hEDS, gastroparesis with a gastrojejunal feeding tube, POTS, and SSS with a pacemaker presented with intractable nausea and vomiting. She had a prior diagnosis of gastroparesis confirmed by a gastric emptying study. She had undergone extensive outpatient and inpatient trials of both standard and atypical antiemetics and prokinetics without meaningful relief. She was hospitalized for nearly a month for symptomatic and nutritional support, with no clear cause on imaging.
During admission, a PICC line was placed, and she was started on TPN for nutritional support due to inability to tolerate gastrojejunal (GJ) tube feeds. Additionally, she received a gastric pylorus botulinum toxin injection, which provided minimal relief. The patient was ultimately discharged on TPN with outpatient follow up with GI for G-POEM procedure.
The patient underwent an uncomplicated G-POEM procedure. Within one month, the patient reported improvement in her nausea and oral intake and was weaning herself off TPN while gaining weight.
Discussion
Gastroparesis in patients with hEDS is likely multifactorial, involving autonomic dysfunction, visceral smooth muscle impairment, and connective tissue abnormalities. In this case, the patient received extensive pharmacological therapies and pyloric botulinum toxin without substantial benefit, ultimately requiring TPN. 
G-POEM, a minimally invasive procedure that cuts the pyloric sphincter muscle, is gaining popularity as a treatment for refractory gastroparesis. Although its role in hEDS is still under investigation, this case highlights its potential benefit, especially in cases where patients fail medical management and require nutritional support


Refractory gastroparesis in a patient with Ehlers-Danlos Syndrome: Symptomatic improvement following G-POEM

Authors:
Paola P. Colón Terrón, B.S. 1,3, Linda Pérez, , DrPH, MSc 1,3, Elinette M. Albino, , MT(ASCP), PhD, MS 2,3
1 San Juan Bautista School of Medicine 2 School of Health Professions, University of Puerto Rico Medical Science Campus 3 Puerto Rico Genetics Laboratory

Abstract Title:
Subclinical Elevations of C5DC in Puerto Rican Children with Neurodevelopmental Disorders: Exploring a Potential Metabolic Signature of Neurogenetic Risk

Background:
Glutarylcarnitine (C5DC) is a dicarboxylic acylcarnitine involved in the catabolism of lysine and tryptophan. Its accumulation is typically associated with glutaric acidemia type I (GA1), a rare metabolic disorder. However, in Puerto Rico, a population with a high burden of rare and recessive genetic conditions, C5DC levels have been observed to be consistently elevated in children with neurodevelopmental symptoms, though not reaching the threshold required for a GA1 diagnosis. This pattern raises the possibility that subclinical elevations of C5DC may reflect
an underlying metabolic signature associated with broader neurogenetic risk.

Methods:
We conducted a retrospective analysis of acylcarnitine profiles in a cohort of Puerto Rican pediatric patients (n = 98) with clinical features suggestive of neurogenetic disorders. C5DC levels were measured via tandem mass spectrometry and correlated with clinical phenotypes, neuroimaging findings, and genetic testing results.

Results:
LASSO linear regression with 10-fold cross-validation identified seventeen phenotypes associated with C5DC levels: Bell’s palsy, behavioral delays, encephalopathy, gender, aggressive behavior, hearing loss, hypotonia, epilepsy, developmental disorder of speech, sensory issues, intellectual disability, Charcot-Marie-Tooth disease, and autism spectrum disorder, among others. Post-LASSO linear regression analysis showed statistically significant associations between C5DC levels and behavioral delays (p < 0.010), aggressive behavior (p < 0.05), hearing loss (p < 0.05), epilepsy (p < 0.05), and sensory issues (p < 0.05). Notably, the majority of cases were clustered in the northern region of Puerto Rico, with the top five municipalities being San Juan, Vega Baja, Carolina, Bayamon, and Toa Alta.

Conclusion:
These preliminary findings suggest that subclinical elevations of C5DC may be indicative of neurogenetic vulnerability in Puerto Rican children. C5DC may serve as a metabolic biomarker worthy of further investigation for inclusion in neurogenetic screening panels, especially in genetically isolated populations with known founder effects and high consanguinity. Continued research is needed to elucidate the mechanistic basis of this association and its diagnostic potential.

Subclinical Elevations of C5DC in Puerto Rican Children with Neurodevelopmental Disorders: Exploring a Potential Metabolic Signature of Neurogenetic Risk

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