Authors :
Presenting Author: Rayann Solidum, MS – Stanford
tanya Brown, PHD – Tess Research Foundation; Best Carrie, MPH – Brown University; Sydney Cooper, MS – UT Southwestern; jennifer Elacio, BS – Brown University; Kimberley Goodspeed, MD – UT Southwestern; Judy LIu, MD, PhD – Brown University; Kim Nye, BA – Tess Research Foundation; Sweta Patnaik, MS – Stanford; Emily Spelbrink, MD, PhD – Stanford; Brenda Porter, MD, PhD – Stanford
Rationale:
SLC13A5 Citrate Transporter Disorder (EIEE25), is associated with neonatal onset epilepsy. Patients display multiple neurological symptoms, including motor skill delays and cognitive impairment. The TESS Research Foundation funded a natural history study to characterize the disorders neurologic phenotype, disease progression, and develop outcome measures for future clinical trials.
Methods:
Subjects were identified by the TESS Foundation. Confirmatory genetic testing was required and the study was open to subjects of all ages and clinical status. Here we report interim data from two natural history studies with periodic visits scheduled over a two year period was developed for assessing neuropsychological function for remote subjects (outside the US) and in person (within the US). Age range at time of enrollment was four months to 30 years, average 9.1 years, with 13 males and 11 females. Data from the Vineland Adaptive Behavior Scales edition 3 (VABS-3) on 24 subjects and Mullen Scales of Early Learning (MSEL) and Peabody Developmental Motor Scales, 2nd edition (PDMS-2), on nine subjects are reported. The VABS-3 was administered to all caregivers at the baseline, 6, 12, and the 24 month visits. The in-person study included the VABS-3 and additionally the MSEL and PDMS-2 assessments at the 6, 12, and 24 month visits. All data was entered into Stanford Redcap. Interim data is reported for this ongoing study.
Results:
Fifteen subjects completed at least two VABS-3, 9 at the baseline visit only. Adaptive Behavior Composite (ABC) scores were mostly abnormal, with 17/24 subjects with mild or moderate impairment, three profound impairment, and three in the average category, see Table 1. Over half, 13/24 scored less than a 70-standard score in all five domains, signifying profound and diffuse skill deficits. One was able to receive normal standard scores for all domains. Seven subjects completed the MSEL and PDMS-2 at least twice and two subjects completed both once. All subjects and in every domain of the MSEL and PDMS-2, received a lower age equivalent score compared to their biological age, Table 2. Most subjects VABS-3 ABC scores stayed in the same impairment category over time. The MSEL Composite Standard Score, and the PDMS-2 Total Motor Quotient showed minimal change over time. Interestingly, in all but a single subject visit the receptive language had higher age equivalent scores than expressive language. For the PDMS-2, in all patient visits but one, visual receptive age equivalent was higher than the visual motor age equivalent scores.
Conclusions:
A total of 20 out of 24 subjects had significant abnormalities in adaptive behavior, motor, and language skills. Most subjects have a split in their language skills with reception better than expression, which we suspect is secondary to their profound motor impairment. Within subject scores do not significantly change over the study time points collected to date. The VABS-3, MSEL, and PDMS-2 so far appear to be outcome measures that are impaired and consistent over time and should provide valuable outcome measures for future clinical trials in SLC13A5 Citrate Transporter Disorder.
Funding: TESS Research Foundation