Cerebral Creatine Deficiency Syndrome due to GAMT Deficiency – Importance of Meticulous Developmental Screening: A Case Report

Abstract:

Background:
Cerebral creatine deficiency syndrome (CCDS) is a rare metabolic disorder characterized by creatine deficiency in the brain, leading to developmental delays, intellectual disabilities, and neurological impairments.
Clinical Description:
An 8-month-old girl, born out of a consanguineous marriage, presenting for routine health check-up, was found to have subtle developmental delay with hypotonia, without seizures. As per the Bayley developmental screening tool, she was categorized under “emerging for delay in cognitive, gross motor skills, and risk for delay in fine motor skills, language, and social skills.”
Management and Outcome:
Routine blood tests, blood sugar, thyroid profile, serum ammonia, and lactate were normal. Magnetic resonance (MR) imaging showed T2/FLAIR hyperintensities in white matter including parieto-occipital region, globus pallidus, mid-brain, pons, suggestive of neuro-metabolic disorders. An MR spectroscopy revealed absent creatine peaks, suggestive of CCDS, which was confirmed by identifying a likely pathogenic variant in the guanidinoacetate methyltransferase gene. Creatine and ornithine supplementation led to significant developmental improvement, with the child achieving normal cognitive and motor milestones at 2-year follow-up.
Conclusion:
Routine screening using appropriate developmental screening tools is particularly vital in low-resource settings where metabolic disorders often go undiagnosed. Early diagnosis of CCDS and targeted therapy can result in normal neurodevelopmental outcomes.

Link to article: https://journals.lww.com/ipcr/fulltext/2025/07000/cerebral_creatine_deficiency_syndrome_due_to_gamt.12.aspx?context=latestarticles

PubMed:  https://pmc.ncbi.nlm.nih.gov/articles/PMC7313580/

Authors: David, Allen; Daniel, Nivya Jeet; Jose, Priya; Manokaran, Ranjit Kumar

Key Terms: GAMT, Clinical Study, MRS, Supplements, Diagnostic, Pediatric Patient, Female Patient