We were interested in elucidating the non-neurologic health of patients with autosomal recessive SLC13A5 Citrate Transporter (NaCT) Disorder. Multiple variants have been reported that cause a loss of transporter activity, resulting in significant neurologic impairment, including seizures, as well as motor and cognitive dysfunction. Additionally, most patients lack tooth enamel (amelogenesis imperfecta). However, patients have not had their overall health and growth described in detail. Here we characterized the non-neurologic health of 15 patients with medical records uploaded to Ciitizen, a cloud-based patient medical records portal. Ciitizen used a query method for data extraction. Overall, the patients’ records suggested a moderate number of gastrointestinal issues related to feeding, reflux, vomiting and weight gain and a diverse number of respiratory complaints. Other organ systems had single or no abnormal diagnoses, including liver, renal and cardiac. Growth parameters were mostly in the normal range during early life, with a trend toward slower growth in the few adolescent patients with data available. The gastrointestinal and pulmonary issues may at least partially be explained by the severity of the neurologic disorder. More data are needed to clarify if growth is impacted during adolescence and if adult patients develop or are protected from non-neurologic disorders.

Epileptic encephalopathies may arise from single gene variants. In recent years, next-generation sequencing technologies have enabled an explosion of gene identification in monogenic epilepsies. One such example is the epileptic encephalopathy SLC13A5 deficiency disorder, which is caused by loss of function pathogenic variants to the gene SLC13A5 that results in deficiency of the sodium/citrate cotransporter. Patients typically experience seizure onset within the first week of life and have developmental delay and intellectual disability. Current antiseizure medications may reduce seizure frequency, yet more targeted treatments are needed to address the epileptic and non-epileptic features of SLC13A5 deficiency disorder. Gene therapy may offer hope to these patients and better clinical outcomes than current available treatments. Here, we discuss SLC13A5 genetics, natural history, available treatments, potential outcomes and assessments, and considerations for translational medical research for an AAV9-based gene replacement therapy.

TESS Research Foundation (TESS) is a patient-led nonprofit organization seeking to understand the basic biology and clinical impact of pathogenic variants in the SLC13A5 gene. TESS aims to improve the fundamental understanding of citrate’s role in the brain, and ultimately identify treatments and cures for the associated disease. TESS identifies, organizes, and develops collaboration between researchers, patients, clinicians, and the pharmaceutical industry to improve the lives of those suffering from SLC13A5 citrate transport disorder. TESS and its partners have developed multiple molecular tools, cellular and animal models, and taken the first steps toward drug discovery and development for this disease. However, much remains to be done to improve our understanding of the disorder associated with SLC13A5 variants and identify effective treatments for this devastating disease. Here, we describe the available SLC13A5 resources from the community of experts, to foundational tools, to in vivo and in vitro tools, and discuss unanswered research questions needed to move closer to a cure.

This practice guideline from the American Epilepsy Society provides evidence-based recommendations for pharmacological, dietary, and surgical therapies for epilepsy for infants and children from 1 month of age to <36 months. The multidisciplinary panel updated an existing systematic review, which was funded by the Patient-Centered Outcomes Research Institute and conducted by ECRI (formerly the Emergency Care Research Institute) on behalf of the Agency for Healthcare Research and Quality. The updated review used the same search strategy, inclusion/exclusion criteria, and Grading of Recommendations Assessment, Development and Education methodology, and added studies from August 2021 through September 2025 that were not in the original systematic review. As with the previous review, West syndrome and infantile spasms were excluded from this guideline, as existing treatment guidance is already available for infantile epileptic spasms. While many of the recommendations are conditional due to low certainty of evidence, the panel made two strong recommendations: (1) hemispherectomy/hemispherotomy surgery is recommended for infants and children <36 months of age with drug resistant epilepsy secondary to select underlying lesional pathologies, including but not limited to hemimegaloencephaly, Rasmussen's encephalitis, Sturge-Weber syndrome, perinatal stroke, and hemispheric cortical dysplasia; and (2) intralobar, multilobar, or focal resections or posterior disconnections for drug-resistant focal or lesional epilepsy in this same age range. A treatment algorithm was developed based on evidence and expert opinion as part of the guideline to help place pharmacological, dietary, and surgical recommendations in a clinical context. The limited number of studies and low certainty of evidence in this population underscores the need for higher-quality data and etiology-specific treatments. More research is needed to evaluate effective therapies for infants with epilepsy, as well as the impact these therapies have on long-term developmental and mortality outcomes.

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.