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.

Quality of Life of Primary Caregivers of Children With Cerebral Palsy From a Family Perspective.

BACKGROUND: Cerebral palsy is a heterogeneous group of permanent non-progressive disorders affecting the development of movement and posture, varying in severity, interfering with daily activity, and associated with multiple comorbidities. Previous studies in different regions of Saudi Arabia have shown links between caregivers' mental health and children's well-being. However, the lack of such research in the Tabuk region necessitates the development of a new survey to assess caregivers' quality of life in this specific area. METHODOLOGY: This was a cross-sectional study, conducted during 2022-2023. It included the caregivers of Saudi children with cerebral palsy in the Tabuk region. Data was collected using an online questionnaire and was analyzed using the SPSS program (IBM Corp., Armonk, NY). RESULTS: The study included 63 participants. Mothers (50.8%) and fathers (46.0%) were the primary caregivers. The comorbidities of cerebral palsy children like seizures (28.6%) and learning difficulties (19.0%) were prevalent for cerebral palsy children. Around 20.6% of participants received home health care. In terms of family quality of life, the majority expressed satisfaction with family interaction, parenting, and emotional well-being, although mixed feelings were observed. CONCLUSION: The majority of caregivers reported satisfaction in various domains of family quality of life, particularly in family interaction and parenting. However, a notable percentage expressed dissatisfaction in some areas, highlighting the complex emotional and practical challenges faced by these caregivers.