Developmental trajectories of 31 French Creatine Transporter Deficiency (SLC6A8) patients: New insights into outcome measures selection

Abstract

Objective: Creatine Transporter Deficiency (CTD) is a rare genetic disorder related to SLC6A8 gene mutations and leading to Intellectual Disability (ID). The present work aims at a more precise description of the developmental trajectories and key clinical features associated with SCL6A8 gene mutations, and the identification of objective reliable outcome measures for future clinical trials as new therapeutic avenues are emerging. Methods: This study was part of a National Clinical Research Program on X-linked ID. All CTD patients were clinically reviewed. Exhaustive clinical data were collected. Cognitive, adaptive and behavioral assessments were performed. We also assessed the impact of CTD on primary caregiver. Results: 31 French CTD patients were included: 27 males/4 females. The mean age was 11.4 years [3.2–23.8]. There was a strong correlation between the age at diagnosis and the age of CTD patients (r2=0.7, p<0.001): the younger the patients were, the earlier the diagnosis was made. 20.8% had microcephaly at birth. Mean age at walking alone in males was 2.2 years [1.17–4]. Only one patient out of 31 was unable to walk without help. 81.5% of CTD patients could use the thumb-index pinch (mean age=2.28 years [0.8–4.8]). Only 44.4% of male CTD patients were able to combine two words (mean age=4.9 years [4–5.5]). 45.2% of CTD patients had seizures. 10/31 patients had amyotrophy. Early onset behavioral troubles were observed in 82%. It was impossible to perform a Wechsler scale in 75%, whereas a Peabody Picture Vocabulary Test was possible in 54% of the patients (mean vocabulary age=3.4 years [1.75–6.25]). Vineland Adaptive Behavioral Scale revealed a mean global adaptive standard score of 56 (SD=9.9). Conclusion: We characterized the developmental trajectory of CTD patients. Vineland and PPVT scales might be useful for future trials, but new outcome measures appropriate for CTD patients (such as eye-tracking) should be developed.