Background/Objectives: The evolving capabilities of large language models, such as generative pre-trained transformers (ChatGPT), offer new avenues for disseminating health information online. These models, trained on extensive datasets, are designed to deliver customized responses to user queries. However, as these outputs are unsupervised, understanding their quality and accuracy is essential to gauge their reliability for potential applications in healthcare. This study evaluates responses generated by ChatGPT addressing common patient concerns and questions about cleft lip repair. Methods: Ten commonly asked questions about cleft lip repair procedures were selected from the American Society of Plastic Surgeons’ patient information resources. These questions were input as ChatGPT prompts and five board-certified plastic surgeons assessed the generated responses on quality of content, clarity, relevance, and trustworthiness, using a 4-point Likert scale. Readability was evaluated using the Flesch reading ease score (FRES) and the Flesch–Kincaid grade level (FKGL). Results: ChatGPT responses scored an aggregated mean rating of 2.9 out of 4 across all evaluation criteria. Clarity and content quality received the highest ratings (3.1 ± 0.6), while trustworthiness had the lowest rating (2.7 ± 0.6). Readability metrics revealed a mean FRES of 44.35 and a FKGL of 10.87, corresponding to approximately a 10th-grade literacy standard. None of the responses contained grossly inaccurate or potentially harmful medical information but lacked citations. Conclusions: ChatGPT demonstrates potential as a supplementary tool for patient education in cleft lip management by delivering generally accurate, relevant, and understandable information. Despite the value that AI-powered tools can provide to clinicians and patients, the lack of human oversight underscores the importance of user awareness regarding its limitations.

Background Multiple Sulfatase Deficiency (MSD) is a rare inherited lysosomal storage disorder characterized by loss of function mutations in the SUMF1 gene that manifests as a severe pediatric neurological disease. There are no available targeted therapies for MSD. Methods We engineered a viral vector (AAV9/SUMF1) to deliver working copies of the SUMF1 gene and tested the vector in Sumf1 knock out mice that generally display a median lifespan of 10 days. Mice were injected as pre-symptomatic neonates via intracerebroventricular administration, or as post-symptomatic juveniles via intrathecal alone or combination intrathecal and intravenous delivery. Cohorts were assessed for survival, behavioral outcomes, and post-mortem for sulfatase activity. Results We show that treatment of neonates extends survival up to 1-year post-injection. Importantly, delivery of SUMF1 through cerebral spinal fluid at 7 days of age alleviates MSD symptoms. The treated mice show wide distribution of the SUMF1 gene, no signs of toxicity or neuropathy, improved vision and cardiac function, and no behavioral deficits. One-year post treatment, tissues show increased sulfatase activity, indicating functional SUMF1. Further, a GLP toxicology study conducted in rats demonstrates favorable overall safety of this approach. Conclusions These preclinical studies highlight the potential of our AAV9/SUMF1 vector, the design of which is directly translatable for clinical use, as a gene replacement therapy for MSD patients.

Background: SLC13A5 Citrate Transporter Disorder is a rare pediatric neurodevelopmental disorder. Patients have epilepsy, developmental disability, and impaired mobility. While sleep disorders are common in children with neurodevelopmental disorders, sleep abnormalities have not been reported in SLC13A5 patients. Methods: Here, we assessed sleep disturbances in patients through caregiver reported surveys and in a transgenic mouse model of SLC13A5 deficiency. A total of 26 patients were evaluated with the Sleep Disturbance Scale for Children three times over a one-year span. Sleep and wake activities were assessed in the SLC13A5 knock-out (KO) mice using wireless telemetry devices. Results: A high burden of clinically significant sleep disturbances were reported in the patients, with heterogeneous symptoms that remained stable across time. While sleep disturbances were common, less than 30% of patients were prescribed medications for sleep. Comparatively, in SLC13A5 KO mice using EEG recordings, significant alterations were found during light cycles, when rodents typically sleep. During the sleep period, SLC13A5 mice had increased activity, decreased paradoxical sleep, and changes in absolute power spectral density, indicating altered sleep architecture in the mouse model. Conclusions: Our results demonstrate a significant component of sleep disturbances in SLC13A5 patients and mice, highlighting a potential gap in patient care. Further investigation of sleep dysfunction and the underlying etiologies of sleep disturbances in SLC13A5 citrate transporter disorder is warranted.

SLC13A5 citrate transporter disorder is a rare epileptic encephalopathy caused by loss-of-function pathogenic variants in the SLC13A5 gene. Loss of sodium/citrate cotransporter (NaCT) function causes a severe early-life epilepsy resulting in lifelong developmental disabilities and increased extracellular citrate. Current antiseizure medications may reduce seizure frequency, yet more targeted treatments are needed to address the epileptic and neurodevelopmental SLC13A5 phenotype. We performed preclinical studies in SLC13A5-deficient (KO) mice evaluating phenotype rescue with adeno-associated virus (AAV) vector carrying a functional copy of the human SLC13A5 gene (AAV9/SLC13A5). Cerebrospinal fluid delivery of AAV9/SLC13A5 decreased extracellular citrate levels, normalized electrophysiologic and sleep architecture abnormalities, and restored resistance to chemically induced seizures and death. Treatment benefits were achieved with administration during early brain development and in young adult mice, indicating therapeutic efficacy across developmental and postdevelopmental stages. Comparison of delivery routes in young adult KO mice showed that higher brain targeting achieved with intra–cisterna magna delivery resulted in greater treatment benefit as compared with intrathecal lumbar puncture delivery. Together, these results support further development of AAV9/SLC13A5 for treating SLC13A5 citrate transporter disorder.