Creatine deficiency syndromes.

Area of Science:

• Neuroscience
• Metabolic Disorders
• Genetics

Background:

• Central nervous system creatine deficiency leads to severe, treatable neurological diseases.
• Three inherited defects (AGAT, GAMT, CrT) disrupt creatine synthesis and transport, collectively termed creatine deficiency syndromes (CDS).
• CDS may be the most common metabolic disorders with a neurological phenotype, often under-diagnosed.

Purpose of the Study:

• To review the clinical presentation, diagnosis, and treatment of creatine deficiency syndromes (CDS).
• To highlight the significance of CDS as a treatable cause of neurological impairment.
• To emphasize the need for increased consideration of CDS in diagnostic workups.

Main Methods:

• Review of inherited defects in creatine synthesis (AGAT, GAMT) and transport (CrT).
• Analysis of clinical symptoms including developmental delays, seizures, and speech impairment.
• Biochemical analysis of creatine, guanidinoacetate, and creatinine in body fluids.

Main Results:

• AGAT and GAMT deficiencies are autosomal recessive, treatable with good outcomes if initiated early.
• CrT deficiency is X-linked, potentially a frequent cause of X-linked mental retardation, with treatment still under investigation.
• Patients present with global developmental delays, intellectual disability, speech issues, seizures, movement disorders, and autism spectrum disorder.

Conclusions:

• Creatine deficiency syndromes are under-diagnosed but represent a frequent, treatable cause of neurological and cognitive impairment.
• Consideration of CDS is crucial in the workup for genetic intellectual disability, intractable seizures, and speech disorders.
• Prompt diagnosis and intervention, especially in infancy, are key to improving outcomes for AGAT and GAMT deficiencies.