Background. X-linked creatine transporter deficiency (CTD) is a rare genetic metabolic disorder causing significant neurological impairments. It results from mutations in the SLC6A8 gene, which disrupt creatine transport into the brain. Clinical manifestations include developmental delay, intellectual disability, behavioral disorders, and epilepsy, often complicating early diagnosis. The purpose was to summarize current data on the pathogenesis, diagnosis, and treatment of CTD, and to present a clinical case illustrating the diagnostic challenges in this condition. Materials and methods. This article reviews the pathogenesis of CTD, which stems from a deficit in creatine transport to the brain. Diagnosis relies on clinical presentation, biochemical tests (creatine/urine creatinine ratio), and magnetic resonance spectroscopy (MRS), which reveals an absence of creatine peaks in the brain. The gold standard for diagnosis is molecular genetic testing (whole exome sequencing — WES). We present a clinical case of drug-resistant epilepsy and developmental delay in a boy whose CTD diagnosis was confirmed by WES and MRS. Results. Early diagnosis and timely initiation of therapy are crucial for improving prognosis. While no standardized treatment exists, combination therapy with creatine, L-arginine, and glycine proves more effective than creatine alone, as creatine precursors can utilize alternative pathways of transport into the brain. Promising avenues include the development of lipophilic creatine analogs and chaperone therapy. Conclusions. CTD is a serious condition requiring high awareness among clinicians for timely diagnosis. Combined supplementation with creatine and its precursors is the most evidence-based treatment strategy. Further research into novel therapeutic approaches, such as gene therapy, is vital for future treatment.
Antypkin et al. (Sun,) studied this question.