Treatment outcome of creatine transporter deficiency: international retrospective cohort study

Abstract: To evaluate the outcome of current treatment for creatine transporter (CRTR) deficiency, we developed a clinical severity score and initiated an international treatment registry. An online questionnaire was completed by physicians following patients with CRTR deficiency on a treatment, including creatine and/or arginine, and/or glycine. Clinical severity score included 1) global developmental delay/intellectual disability; 2) seizures; 3) behavioural disorder. Phenotype scored 1–3 = mild; 4–6 = moderate; and 7–9 = severe. We applied the clinical severity score 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 phenotype ranged from mild to severe in patients diagnosed at or before 2 years of age or older than 6 years of age. The phenotype ranged from mild to severe in patients with mildly elevated urine creatine to creatinine ratio. Fourteen patients were on the combined creatine, arginine and glycine therapy. On the combined treatment with creatine, arginine and glycine, none of the males showed either deterioration or improvements in their clinical severity score, whereas two females showed improvements in the clinical severity score. Creatine monotherapy resulted in deterioration of the clinical severity score in one male. There seems to be no correlation between phenotype and degree of elevation in urine creatine to creatinine ratio, genotype, or age at diagnosis. Combined creatine, arginine and glycine therapy might have stopped disease progression in males and improved phenotype in females.

Parent Summary: Bruun et al. surveyed the physicians of 17 patients with CTD (from 16 unrelated families) on the severity of each patient’s (1) global developmental delay/intellectual disability, (2) seizures, and (3) behavioral disorders. All patients showed global developmental delays/intellectual disabilities; 8 had seizures; 9 had behavioral disorders (with autism spectrum disorder and ADHD being the most common). The authors derived an overall severity score phenotype (which refers to a set of observable traits) by collapsing the 3 individual severity scores: 7 patients had a “mild” phenotype; 6 patients had a “moderate” phenotype; 4 patients had a “severe” phenotype. There was no correlation between overall severity score and age of diagnosis or between overall severity score and urine creatine:creatinine levels. The authors suggested that while combined creatine, arginine, and glycine therapy might have stopped the progression of the disease in males and might have improved the phenotype in females, the overall severity score did not considerably change during treatment.

Link to article: https://link.springer.com/article/10.1007%2Fs11011-018-0197-3

PubMed: https://pubmed.ncbi.nlm.nih.gov/29435807/

Authors: Theodora U. J. Bruun, Sarah Sidky, Anabela O. Bandeira, Francoise-Guillaume Debray, Can Ficicioglu, Jennifer Goldstein, Kairit Joost, Dwight D. Koeberl, Diogo Luísa, Marie-Cecile Nassogne, Siobhan O’Sullivan, Katrin Õunap, Andreas Schulze, Lionel van Maldergem, Gajja S. Salomons & Saadet Mercimek-Andrews

Key Terms: CTD, Clinical Study, Supplements, Diagnostic