[Clinical characterisation of creatine transporter deficiency associated with SLC6A8 gene variants].

To analyze the clinical features of creatine transporter(CRTR) deficiency associated with SLC6A8 gene variants. The clinical data (clinical presentation, brain imaging, creatine metabolism test and gene variants) of 5 patients admitted to Beijing Children's Hospital, Capital Medical University and diagnosed with CRTR deficiency associated with SLC6A8 gene variants from January 2016 to June 2024 were retrospectively analyzed. A total of 5 patients, all male, presented with the onset of the disease at 1 year and 1 month old to 1 year and 10 months old, and diagnosis at 1 year and 3 months to 9 years old. All patients exhibited varying degrees of intellectual and physical developmental deficits, with autistic-like behaviors present in 2 patients and convulsive episodes present in 4 patients. The brain magnetic resonance imaging, of all 5 patients showed either poor or slightly delayed myelination. Additionally, the brain magnetic resonance spectroscopy (MRS) imaging of 5 patients all showed decreased creatine peaks, and 4 patients had elevated urinary creatine levels indicated by blood and (or) urine creatine metabolism tests. There were 3 patients completed blood creatinine tests, all indicating reduction. Whole-exome sequencing was conducted on all 5 patients, and 4 unreported novel variants were identified: c.371G>C, c.1017-1G>A, c.912+1G>T and c.1016+2T>A. Following treatment with creatine, arginine, and glycine supplementation, no significant advancement was observed in motor and language development. CRTR deficiency associated with SLC6A8 gene variants manifests as developmental delay with or without seizures, with atypical clinical features, the presence of decreased blood creatinine levels and elevated urinary creatine levels. Combined with brain MRS and genetic testing results, patients can be diagnosed.