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.