Creatine Deficiency Syndromes: Clinical Spectrum, Neuroimaging Features and Treatment Response

Creatine deficiency syndromes (CDS) are rare inborn errors of creatine biosynthesis or transport, predominantly affecting the central nervous system. This study aimed to evaluate the clinical features, neuroimaging findings, cardiac involvement and treatment outcomes of patients with CDS, while also increasing awareness of CDS in the differential diagnosis of autism spectrum disorder and developmental delay.

Patients diagnosed with CDS and followed at the Pediatric Metabolism Departments of Çukurova University and Adana City Hospital between 2014 and 2024 were retrospectively analysed. Demographic data, age at symptom onset and diagnosis, clinical findings, laboratory results, brain magnetic resonance imaging, magnetic resonance spectroscopy, genetic analyses, cardiological evaluations and treatment outcomes were recorded.

Eight patients were included: two with arginine-glycine amidinotransferase (AGAT) deficiency, four with guanidinoacetate methyltransferase (GAMT) deficiency and two with creatine transporter deficiency (CTD). Developmental and speech delay were present in all patients. Seizures were observed in six patients and were controlled with antiepileptic therapy. Behavioural disorders, including autistic features, were detected in five patients. Brain MRS revealed reduced cerebral creatine peaks in evaluated patients. Cardiac evaluations showed no abnormalities in any patient. Follow-up MRS performed after treatment initiation in six patients demonstrated a marked increase in cerebral creatine peaks in three patients.

CDS should be considered in patients with unexplained neurodevelopmental delay, epilepsy and autistic features. Early diagnosis and timely treatment are associated with improved outcomes.