Longitudinal Characterization of Males With X-Linked Creatine Transporter Deficiency: Final Results of a Multiyear Observational Study.

backgroundThe purpose of the Vigilan observational study (ClinicalTrials.gov, NCT02931682) was to prospectively assess the natural history and developmental course of creatine transporter deficiency (CTD).

methodsMales with CTD aged 6 months to 65 years were evaluated at 6-month intervals for up to 4 years. Evaluations included neurodevelopmental assessments of intellectual functioning, adaptive functioning, challenging behaviors and the onset and progression of medical comorbidities.

resultsFifty 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 nonfebrile 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 (i.e., 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.

conclusionsIn this cohort, CTD was associated with significant and persistent intellectual disability. The use of absolute metrics from neurodevelopmental tests (e.g., person ability scores) allowed for the quantification of slow, but present, skill development.