Ineffectiveness of creatine, glycine, and arginine supplementation in a female with creatine transporter deficiency: A case report

Abstract: Background: Creatine transporter deficiency (CTD), caused by pathogenic variants of the SLC6A8 gene, is a significant cause of X-linked neurodevelopmental disorders. Heterozygous female patients with CTD exhibit residual creatine transporter activity. Therefore, supplementation therapy with creatine, arginine, and glycine is hypothesized to elevate cerebral creatine levels and improve clinical symptoms. Case presentation: We describe the case of a 12-year-old Japanese girl diagnosed with CTD using genetic analysis and magnetic resonance spectroscopy (MRS). The patient presented with intellectual disabilities, behavioral disturbances, and drug-resistant epilepsy. Supplementation therapy with creatine (400 mg/kg/day), glycine (200 mg/kg/day), and arginine (200 mg/kg/day) led to an increase in cerebral creatine levels as measured by MRS; however, no clinical improvement was observed in her seizures and behavioral symptoms. Discussion: Previously reported cases revealed variability in responses to supplementation therapy among female patients with CTD. Although the factors underlying the differences in therapeutic efficacy remain unclear, higher doses of arginine may be correlated with improved outcomes. Standardized quantitative evaluations using MRS could facilitate more accurate predictions of the efficacy of supplementation therapy. Conclusion: This case highlights the complexities involved in managing female patients with CTD and underscores the need for standardized treatment and evaluation protocols. International collaboration is crucial for developing optimized therapeutic strategies for this rare condition.

Parent Summary: This case study describes a 12-year-old girl with creatine transporter deficiency (CTD). She presented with intellectual disability, behavioral issues, and drug-resistant epilepsy. Although supplementation with creatine, arginine, and glycine successfully increased her brain creatine levels, it did not improve her clinical symptoms. Supplementation was therefore discontinued after 18 months and her symptoms remained unchanged. The authors compared this patient’s results with others reported in the scientific literature, highlighting the variability in treatment response among female CTD patients. Based on other studies, higher arginine doses might be more effective. It emphasizes the importance of using magnetic resonance spectroscopy (MRS) to monitor treatment and calls for standardized, collaborative approaches to improve care for females with CTD.

Link to article: https://www.sciencedirect.com/science/article/pii/S2950221725000212

Authors: Mayuka Tsuchida, Kyoko Takano, Masaru Nasuno, Manami Yabe, Makoto Nishioka, Takenori Natsume, Tomoki Kaneko, Tetsuhiro Fukuyama

Key Terms: CTD, Clinical Study, Diagnostic, MRS, Supplements, Pediatric Patient, Female Patient