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Abstracts

Assessment of Quality of Life and Sleep Disorders in SLC13A5 Deficiency Disorder

Abstract number : 1.449
Submission category : 12. Genetics / 12A. Human Studies
Year : 2023
Submission ID : 1248
Source : www.aesnet.org
Presentation date : 12/2/2023 12:00:00 AM
Published date :

Authors :
Presenting Author: Can Ozlu, MD – University of Texas Southwestern Medical Center

Raegan Adams, PhD candidate – University of Texas Southwestern Medical Center; Tanya Brown, PhD – TESS Research Foundation; Kimberly Nye, Ms – TESS Research Foundation; Judy liu, MD PhD – Brown University; Brenda Porter, MD PhD – Stanford University; Rachel Bailey, PhD – University of Texas Southwestern Medical Center; Kimberly Goodspeed, MD – University of Texas Southwestern Medical Center

Rationale: The SLC13A5 gene encodes a citrate transporter, the loss of which causes an autosomal recessive deficiency disorder 1,2. SLC13A5 deficiency disorder (SDD) presents as a severe infantile epilepsy with multifocal convulsive and subclinical seizures in the first week of life 1 followed by variable seizure burden later in life 3, along with profound developmental disability 1, and tooth mineralization abnormalities 4. There are no studies assessing quality of life (QoL) in SDD patients, which is of interest for clinical prognostication as well as for future clinical trials 5,6. Here, we use standardized tools to assess QoL and sleep problems in this genetic epilepsy.

Methods: We analyzed deidentified data from three caregiver questionnaires, the Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM) and Epilepsy Module (PedsQL-Epi) and the Sleep Disturbance Scale for Children (SDSC) obtained in a multisite SDD natural history study (domestic) and international longitudinal registry at baseline, 6 and 12 month follow-up (n=25). To assess age – score correlation, Spearman test was used. For comparison of scores between baseline and follow-up, Kruskal-Wallis and Friedman tests were utilized. To assess discrepancies across cohorts, Mann-Whitney and Kolmogorov-Smirnov tests were used. Bonferroni correction was used for multiple comparisons.

Results: Baseline scores on the PedsQL-Epi and PedsQL-FIM were markedly low, with lowest scores in cognitive functioning on PedsQL-Epi and worry/daily living in PedsQL-FIM (Fig 1). The median scores on the PedsQL-Epi were 33.3 (95% CI [20.8-41.7]) for impact dimension, 25 (95% CI [0-40]) for cognitive functioning, 50 (95% CI [37.5-50]) for sleep/fatigue, 31.2 (95% CI [12.5-50]) for executive functioning, and 60 (95% CI [45-70]) for mood/behavior. Medians for the baseline PedsQL-FIM summary scores were: 47.9 (95% CI [41.7-61]) for total, 52.5 (95% CI [45-66.2]) for health-related quality of life (HRQL), and 50 (95% CI [43.7-53.1]) for family functioning. The baseline SDSC showed most patients significantly affected (level 3 or above) by disorders of initiating and maintaining sleep (52%), and sleep-wake transition disorders (32%), and the least by disorders of excessive somnolence (8%) (Fig 2). There was no significant change in the scores from baseline to 6 and 12 month follow-up on any of the three measures. No statistically significant correlation with age was observed in any score, although there was a trend towards improved emotional functioning scores in PedsQL-FIM and sleep/fatigue scores in PedsQL-Epilepsy with increasing age. There was no statistically significant difference between domestic and international cohorts.

Conclusions: PedsQL-Epi and PedsQL-FIM scores were strikingly low, remained stable over one year and across ages, and cohorts, demonstrating a significant negative impact of SDD on the QoL of the patient and family and SDSC showed a significant portion of patients with sleep disorders.

Funding: This study was funded by the TESS Research Foundation.

Genetics