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

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Creatine deficiency syndromes (CDS) are rare genetic disorders affecting creatine metabolism.
• These conditions primarily impact the central nervous system, leading to significant neurodevelopmental challenges.
• CDS are often underdiagnosed and can be mistaken for autism spectrum disorder or general developmental delay.

Purpose of the Study:

• To investigate the clinical spectrum of CDS, including neuroimaging and cardiac findings.
• To evaluate the effectiveness of treatment interventions for patients with CDS.
• To raise awareness of CDS as a differential diagnosis for neurodevelopmental disorders.

Main Methods:

• Retrospective analysis of eight patients diagnosed with CDS (AGAT, GAMT, or CTD).
• Data collected included clinical features, neuroimaging (MRI, MRS), genetic analysis, and treatment outcomes.
• Cardiac evaluations were performed to assess for potential involvement.

Main Results:

• All patients presented with developmental and speech delay; six experienced seizures, controlled with medication.
• Five patients exhibited behavioral issues, including autistic features.
• Brain magnetic resonance spectroscopy (MRS) showed reduced creatine levels, which improved with treatment in some patients. No cardiac abnormalities were detected.

Conclusions:

• CDS should be considered in the differential diagnosis of unexplained neurodevelopmental delay, epilepsy, and autistic features.
• Early identification and prompt treatment of CDS are associated with better clinical outcomes.
• This study highlights the importance of recognizing CDS for timely intervention and improved prognosis.