Clinico-radiological features, molecular spectrum, and identification of prognostic factors in developmental and epileptic encephalopathy due to inosine triphosphate pyrophosphatase (ITPase) deficiency

Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects. Exome sequencing was performed to identify underlying ITPA pathogenic variants. Brain MRI (magnetic resonance imaging) scans were systematically analyzed to delineate the neuroradiological spectrum. Survival curves according to the Kaplan–Meier method and log-rank test were used to investigate outcome predictors in different subgroups of patients. We identified 18 distinct ITPA pathogenic variants, including 14 novel variants, and two deletions. All subjects showed profound developmental delay, microcephaly, and refractory epilepsy followed by neurodevelopmental regression. Brain MRI revision revealed a recurrent pattern of delayed myelination and restricted diffusion of early myelinating structures. Congenital microcephaly and cardiac involvement were statistically significant novel clinical predictors of adverse outcomes. We refined the molecular, clinical, and neuroradiological characterization of ITPase deficiency, and identified new clinical predictors which may have a potentially important impact on diagnosis, counseling, and follow-up of affected individuals

Clinico-radiological features, molecular spectrum, and identification of prognostic factors in developmental and epileptic encephalopathy due to inosine triphosphate pyrophosphatase (ITPase) deficiency.

Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects. Exome sequencing was performed to identify underlying ITPA pathogenic variants. Brain MRI (magnetic resonance imaging) scans were systematically analyzed to delineate the neuroradiological spectrum. Survival curves according to the Kaplan-Meier method and log-rank test were used to investigate outcome predictors in different subgroups of patients. We identified 18 distinct ITPA pathogenic variants, including 14 novel variants, and two deletions. All subjects showed profound developmental delay, microcephaly, and refractory epilepsy followed by neurodevelopmental regression. Brain MRI revision revealed a recurrent pattern of delayed myelination and restricted diffusion of early myelinating structures. Congenital microcephaly and cardiac involvement were statistically significant novel clinical predictors of adverse outcomes. We refined the molecular, clinical, and neuroradiological characterization of ITPase deficiency, and identified new clinical predictors which may have a potentially important impact on diagnosis, counseling, and follow-up of affected individuals

Medical students’ perception of the learning environment at King Saud University Medical College, Saudi Arabia, using DREEM Inventory

Mona M Soliman,1,2 Kamran Sattar,2 Sami Alnassar,3 Faisal Alsaif,4 Khalid Alswat,5 Mohamed Alghonaim,6 Maysoon Alhaizan,7 Nawaf Al-furaih7 1Department of Physiology, 2Department of Medical Education, 3Department of Surgery, College of Medicine, King Saud University, 4Department of Surgery, King Saud University Medical City, 5Department of Internal Medicine, 6Department of Medicine, 7College of Medicine, King Saud University, Riyadh, Saudi Arabia Background: The students’ perception of the learning environment is an important aspect for evaluation and improvement of the educational program. The College of Medicine at King Saud University (KSU) reformed its curriculum in 2009 from a traditional to a system-oriented hybrid curriculum.Objective: The objective of the present study was to determine the perception of the second batch (reformed curriculum) of medical graduates about the educational environment at the College of Medicine, KSU, using the Dundee Ready Education Environment Measure (DREEM) scale.Methods: The fifth year medical students were asked to evaluate the educational program after graduation in May 2014. The questionnaire was distributed to the graduate students electronically. The DREEM questionnaire consisted of 50 items based on Likert’s scale; and five domains, namely, students’ perceptions of learning, perceptions of teachers, academic self-perceptions, perceptions of atmosphere, and social self-perceptions. Data were analyzed using SPSS.Results: A total of 62 students participated in the study. The score for students’ perception of learning among medical students ranged from 2.93 to 3.64 (overall mean score: 40.17). The score for students’ perception of teachers ranged from 2.85 to 4.01 (overall mean score: 33.35). The score for students’ academic self-perceptions ranged from 3.15 to 4.06 (overall mean score: 28.4). The score for students’ perception of atmosphere ranged from 2.27 to 3.91 (overall mean score: 41.32). The score for students’ social self-perceptions ranged from 2.85 to 4.33 (overall mean score: 24.33). The general perceptions of the students in all five sub-scales were positive.Conclusion: The overall student’s perception about the educational environment was satisfactory. This study was important to evaluate the students’ perception of the learning environment among medical graduates of the reformed curriculum and provided guidance on areas of improvement in the curriculum. Keywords: medical students, perception, learning environment, DREEM inventory, Saudi Arabi