To enhance understanding of symptoms and developmental course of people living with CTD, contribute to development of therapeutic intervention programs, and identify potential study endpoints relevant to CTD.

Little is known about the natural history of CTD, an X-linked disorder of disrupted creatine transport into cells.

This study (NCT02931682) used parent questionnaires and clinical assessments to characterize clinical features of males with confirmed CTD (SLC6A8 pathogenic variant) for up to 4 years.

Fifty patients (mean baseline age, 8.8 years; range, 1.5-24.4 years) were enrolled. Mean age at first symptom was 9.0 months, mean time from initial evaluation to diagnosis was 3.2 years, and mean CTD diagnosis age was 4.9 years. In addition to global developmental delay, medical history included seizures (68%), hypotonia (decreased muscle tone; 50%), aggressive behavior (46%), self-injurious behavior (40%), autism spectrum disorder features (32%), attention deficit disorder (32%), anxiety disorder (20%), and cardiac arrhythmia (8%). Baseline language levels were single words (42%), sentences (33%), babbling (15%), no speech (4%), and unknown (4%). Behaviorally, based on the ABC-2 questionnaire, patients with CTD often exhibited irritability and hyperactivity. Baseline gastrointestinal symptoms included constipation (44%), choking/gagging (32%), vomiting (16%), and gastroesophageal reflux disease (12%). Across measures, little change or improvement was seen over time.