Longitudinal Characterization of Males with X-Linked Creatine Transporter Deficiency: Final Results of a Multi-Year Observational Study

Abstract: Purpose
The purpose of the Vigilan observational study (ClinicalTrials.gov, NCT02931682) was to prospectively assess the natural history and developmental course of creatine transporter deficiency (CTD).
Methods
Males with CTD aged 6 months to 65 years were evaluated at six-month intervals for up to 4 years. Evaluations included neurodevelopmental assessments of intellectual functioning, adaptive functioning, and challenging behaviors and the onset and progression of medical comorbidities.
Results
Fifty participants (median age, 7.6 years) were enrolled. The predominant CTD phenotype consisted of significant intellectual disabilities and limited skill development over time. Most participants had a history of febrile or non-febrile seizures, gastrointestinal symptoms, and growth failure. All participants learned how to walk, 78% developed at least some verbal speech, and 34% communicated using phrases or sentences. Norm-referenced neurodevelopment assessments indicated declining standardized scores over time; however, absolute scores (ie, age equivalent person ability scores) indicated that developmental gains were slower than average, particularly among older participants. Between-person differences in neurodevelopmental skills as a function of age did not match within-person change, suggesting a cohort effect.
Conclusion
In this cohort, CTD was associated with significant and persistent intellectual disability. The use of absolute metrics from neurodevelopmental tests (eg, person ability scores) allowed for the quantification of slow, but present, skill development.

Link to article: https://www.sciencedirect.com/science/article/pii/S0887899425003248

Authors: Judith S. Miller, Cristan Farmer, Susan Blair, Simona Bianconi, Natacha Akshoomoff, Irina Anselm, Bruce A. Barshop, Lindsey Becker, Amanda E. Bennett, Leandra N. Berry, Elizabeth M. Berry-Kravis, Aleksandra Bruchey, Anna W. Byars, Tricia Cimms, Kim M. Cecil, Maxine Covello, Laura S. Cubit, Tanvi Das, Robert J. Davis, Madison Drye, Can Ficicioglu, John B. Fulton, Robin P. Goin-Kochel, Whitney Guthrie, Barbara E. Hallinan, Fady Hannah-Shmouni, Kathryn E. Gustafson, Dwight D. Koeberl, Nicola Longo, Eva Mamak, Saadet Mercimek-Andrews, Claire Michalak, Forbes D. Porter, Samar Rahhal, Linda Rees, Gail A. Spiridigliozzi, Caitlin Stone, Nancy R. Sullivan, V.Reid Sutton, Rebecca P. Thomas, Manisha Udhnani, Susan Waisbren, Michelle Xu, Lin Zhang, Melanie Brandabur, Audrey Thurm

Key terms: CTD, Pediatric Patient, Male Patient