Conditions · Metabolism (biochemistry)
Guanidinoacetate methyltransferase (GAMT) deficiency !
The body cannot finish making creatine and a toxic precursor builds up: delay, seizures and autism-like behaviour. Early creatine helps.
Updated 2026-11-01
Structures involved
Tap one to see what it is and open it in 3D.
In biochemistry
What it is
An inherited creatine deficiency syndrome caused by lack of guanidinoacetate methyltransferase (gene GAMT), the second enzyme of creatine synthesis.
Who gets it
Very rare: about 80 affected people had been described, about a third of Portuguese origin. Some newborn screening programmes now include it. No Colombian figures are published.
Causes
- Autosomal recessive variants in GAMT
Risk factors
- Carrier parents; consanguinity
- Affected sibling
Pathophysiology
GAMT methylates guanidinoacetate with SAM to form creatine. Without it, creatine and phosphocreatine are very low in brain and muscle, so the brain's energy buffering fails. Guanidinoacetate accumulates in blood, urine and brain, where it is neurotoxic and lowers the seizure threshold (it acts on GABA-A receptors).
Symptoms and signs
- Developmental delay, especially of speech
- Intellectual disability
- Seizures
- Autistic or hyperactive behaviour, self-injury
- Involuntary movements (dystonia, chorea) in some
Diagnosis
- Clinical
- Child with global or speech delay, seizures and behaviour problems without another explanation.
- Tests
- High guanidinoacetate and low creatine (and creatinine) in plasma and urine; enzyme activity in fibroblasts or lymphoblasts; GAMT gene testing.
- Imaging
- Brain MR spectroscopy with an absent or very low creatine peak; MRI may show globus pallidus signal changes.
Treatment
- Medical
- Oral creatine supplements to refill brain creatine, as directed by the metabolic team
- Lifestyle
- Arginine-restricted diet to reduce guanidinoacetate production
- Medical
- Ornithine supplements, which inhibit AGAT and lower guanidinoacetate
- Rehabilitation
- Speech, behavioural and educational therapies
- Follow-up
- Monitoring of guanidinoacetate levels, seizures and development
Complications
- Permanent intellectual disability when treatment starts late
- Drug-resistant epilepsy
Prognosis
Treatment started before symptoms (for example after newborn screening) can allow near-normal development; late treatment improves seizures and behaviour more than intellect.
Test yourself
Think of the answer, then tap the question to see it.
Which reaction is blocked in GAMT deficiency?
The methylation of guanidinoacetate by SAM to form creatine.
Which compound accumulates and why is it harmful?
Guanidinoacetate, which is neurotoxic and lowers the seizure threshold.
What does brain MR spectroscopy show?
An absent or very low creatine peak.
Why is ornithine given in GAMT deficiency?
Ornithine inhibits AGAT, the first enzyme of creatine synthesis, so less guanidinoacetate is made.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Guanidinoacetate methyltransferase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); GAMT gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.
