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Background: This retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA., Methods: Medical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently., Results: Eighty-five individuals with UCD were included in the analyses. Fifty-six of the 85 patients (66%) experienced HA crises, with a total of 163 HA events. Seizures are observed in 13% of HA events. Among all HA events with concomitant EEG, subclinical seizures were identified in 27% of crises of encephalopathy without clinical seizures and 53% of crises with clinical seizures. The odds of seizures increases 2.65 (95% confidence interval [CI], 1.51 to 4.66) times for every 100 μmol/L increase in ammonia and 1.14 (95% CI, 1.04 to 1.25) times for every 100 μmol/L increase in glutamine., Conclusions: This study highlights the utility of EEG monitoring during crises for patients presenting with clinical seizures or encephalopathy with HA. During HA events, measurement of initial ammonia and glutamine can help determine risk for seizures and guide EEG monitoring decisions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mitochondrial diseases are inherited disorders that impede the mitochondria's ability to produce sufficient energy for the cells. They can affect different parts of the body, notably the brain. Neurological symptoms and epilepsy are prevalent in patients with mitochondrial disorders. The epileptogenicity of mitochondrial disorder is a complex process involving the intricate interplay between abnormal energy metabolism and neuronal activity. Several modalities have been used to detect seizures in different disorders including mitochondrial disorders. EEG serve as the gold standard for diagnosis and localization, commonly complemented by additional imaging modalities to enhance source localization. In the current work, we propose the use of functional near-infrared spectroscopy (fNIRS) to identify the occurrence of epilepsy and seizure in patients with mitochondrial disorders. fNIRS proves an advantageous imaging technique due to its portability and insensitivity to motion especially for imaging infants and children. It has added a valuable factor to our understanding of energy metabolism and neuronal activity. Its real-time monitoring with high spatial resolution supplements traditional diagnostic tools such as EEG and provides a comprehensive understanding of seizure and epileptogenesis. The utility of fNIRS extends to its ability to detect changes in Cytochrome c oxidase (CcO) which is a crucial enzyme in cellular respiration. This facet enhances our insight into the metabolic dimension of epilepsy related to mitochondrial dysfunction. By providing valuable insights into both energy metabolism and neuronal activity, fNIRS emerges as a promising imaging technique for unveiling the complexities of mitochondrial disorders and their neurological manifestations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Neuronal ceroid lipofuscinoses (NCLs) (hereafter described as CLN disease) comprise a rare and life-limiting set of genetically inherited neurodegenerative disorders that are characterized by abnormal lysosomal storage. The NCL disorders are, collectively, the most common group of degenerative brain disorders in children., Patient Descriptions: We report two cases of CLN disease that were diagnosed and treated at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Both cases of CLN disease (CLN1 and CLN6 diagnosed in 2016 and 2017, respectively) profiled in this report presented with clinical features of Rett syndrome. In the first case, a 2-year-old girl presented with Rett-like clinical features, including global developmental regression and hand-wringing action. Single-gene analysis of the MECP2 gene was negative. However, PPT1 gene sequencing revealed a novel homozygous frameshift mutation, c.629_630dupGT (p.Ile211Valfs∗10). In the second case, a 7.5-year-old girl presented with ataxia, progressive myoclonic epilepsy, and Rett-like hand-wringing. A c.794_796delCCT variant in the CLN6 gene was identified by whole-exome sequencing. Fingerprint bodies from electron microscopy of the skin also supported a diagnosis of CLN disease in our second case., Discussion: Presentation with clinical features of Rett syndrome has only been reported in patients diagnosed with CLN1 and CLN7 disease, and never in those with CLN6., Conclusions: Physicians should suspect and investigate for CLN disease in patients with Rett-like phenotype who are negative for MECP2 mutation, especially in patients with visual impairment and early prominent brain atrophy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Congenital central hypoventilation syndrome (CCHS) is a rare condition caused by mutations in the Paired-Like Homeobox 2B (PHOX2B) gene. It causes alveolar hypoventilation and autonomic dysregulation. This report aimed to raise awareness of this rare cause of neonatal apnea and hypoventilation as well as described the diagnostic work up to confirm the diagnosis in resource-limited setting where polysomnography for neonate is unavailable., Case Presentation: A late preterm female newborn born from a non-consanguineous primigravida 31-year-old mother had desaturation soon after birth followed by apnea and bradycardia. After becoming clinically stable, she still had extubation failure from apnea without hypercapnic ventilatory response which worsened during non-rapid eye movement (NREM) sleep. After exclusion of other etiologies, we suspected congenital central hypoventilation syndrome and sent genetic testing. The result showed a PHOX2B gene mutation which confirmed the diagnosis of CCHS. We gave the patient's caregivers multidisciplinary home respiratory care training including tracheostomy care, basic life support, and simulation training for respiratory problem solving. Then, the patient was discharged and scheduled for follow-up surveillance for associated conditions., Conclusion: Diagnosis of CCHS in neonates includes the main clue of the absence of hypercapnic ventilatory response which worsens during non-rapid eye movement (NREM) sleep after exclusion of other causes. Molecular testing for PHOX2B gene mutation was used to confirm the diagnosis., (© 2022. The Author(s).)

The use of rapid DNA sequencing technology in severely ill children in developed countries can accurately identify diagnoses and positively impact patient outcomes. This study sought to evaluate the outcome of Thai children and adults with unknown etiologies of critical illnesses with the deployment of rapid whole exome sequencing (rWES) in Thailand. We recruited 54 unrelated patients from 11 hospitals throughout Thailand. The median age was 3 months (range, 2 days-55 years) including 47 children and 7 adults with 52% males. The median time from obtaining blood samples to issuing the rWES report was 12 days (range, 5-27 days). A molecular diagnosis was established in 25 patients (46%), resulting in a change in clinical management for 24 patients (44%) resulting in improved clinical outcomes in 16 patients (30%). Four out of seven adult patients (57%) received the molecular diagnosis which led to a change in management. The 25 diagnoses comprised 23 different diseases. Of the 34 identified variants, 15 had never been previously reported. This study suggests that use of rWES as a first-tier investigation tool can provide tremendous benefits in critically ill patients with unknown etiology across age groups in Thailand., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)