Treatment outcome of creatine transporter deficiency: international retrospective cohort study

To evaluate the outcome of current treatment for creatinetransporter (CRTR) deficiency, we developed a clinical severityscore and initiated an international treatment registry. An online questionnaire was completed by physicians following patients with CRTR deficiency on a treatment, including creatineand/or arginine, and/or glycine. Clinical severityscore included 1) global developmental delay/intellectual disability; 2) seizures; 3) behavioural disorder. Phenotypescored 1–3 = mild; 4–6 = moderate; and 7–9 = severe. We applied the clinical severityscore pre- and on-treatment. Seventeen patients, 14 males and 3 females, from 16 families were included. Four patients had severe, 6 patients had moderate, and 7 patients had a mild phenotype. The phenotyperanged from mild to severein patients diagnosed at or before 2 years of age or older than 6 years of age. The phenotyperanged from mild to severein patients with mildly elevated urine creatineto creatinine ratio. Fourteen patients were on the combined creatine, arginine and glycinetherapy. On the combined treatment with creatine, arginine and glycine, none of the males showed either deterioration or improvements in their clinical severityscore, whereas two females showed improvements in the clinical severityscore. Creatinemonotherapy resulted in deterioration of the clinical severityscore in one male. There seems to be no correlation between phenotypeand degree of elevation in urine creatineto creatinine ratio, genotype, or age at diagnosis. Combined creatine, arginine and glycinetherapy might have stopped disease progression in males and improved phenotypein females.