Guanidinoacetate methyltransferase deficiency

A rare metabolic disorder affecting creatine synthesis

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Guanidinoacetate methyltransferase deficiency (GAMT deficiency) is a rare autosomal recessive metabolic disorder that affects the body's ability to synthesize creatine, an essential compound for energy storage and utilization in muscle and brain tissues. This condition is characterized by a deficiency in the enzyme guanidinoacetate methyltransferase, which is crucial for the conversion of guanidinoacetate to creatine.

Pathophysiology

Guanidinoacetate methyltransferase deficiency results from mutations in the GAMT gene, which encodes the enzyme responsible for the methylation of guanidinoacetate to form creatine. This enzymatic step is the final stage in the creatine synthesis pathway. The deficiency leads to an accumulation of guanidinoacetate and a depletion of creatine in the body. Elevated levels of guanidinoacetate are neurotoxic and contribute to the neurological symptoms observed in affected individuals.

Clinical Presentation

The clinical manifestations of GAMT deficiency typically appear in infancy or early childhood. Common symptoms include:

• Developmental delay
• Intellectual disability
• Seizures
• Hypotonia
• Movement disorders
• Behavioral problems such as autism spectrum disorder-like features

Diagnosis

Diagnosis of guanidinoacetate methyltransferase deficiency is based on clinical evaluation, biochemical testing, and genetic analysis. Key diagnostic tests include:

• Measurement of guanidinoacetate and creatine levels in urine and blood
• Magnetic resonance spectroscopy (MRS) to assess brain creatine levels
• Genetic testing to identify mutations in the GAMT gene

Treatment

The primary treatment for GAMT deficiency involves dietary supplementation to restore creatine levels and reduce guanidinoacetate accumulation. Treatment strategies include:

• Creatine monohydrate supplementation
• Ornithine supplementation to reduce guanidinoacetate production
• Dietary restriction of arginine and protein to lower guanidinoacetate levels

Early diagnosis and treatment are crucial to improving outcomes and preventing irreversible neurological damage.

Prognosis

With early and appropriate treatment, individuals with GAMT deficiency can experience significant improvements in symptoms and quality of life. However, untreated or late-diagnosed cases may result in severe intellectual disability and persistent neurological issues.

Related pages

• Creatine deficiency syndromes
• Metabolic disorders
• Inborn errors of metabolism