Guanidinoacetate Methyltransferase Deficiency

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Guanidinoacetate Methyltransferase (GAMT) Deficiency is an inherited metabolic disorder that is characterised by neurological and muscular problems. It is caused by defects in the GAMT gene which provides instructions for making the guanidinoacetate methyltransferase enzyme. This enzyme is needed by the body to produce a compound called creatine which is needed to store and utilise energy. The defect causes a deficiency of creatine which leads to the symptoms of this disorder.

We are unsure of the exact prevalence of this disorder. Approximately 110 cases have been reported in the medical literature. It is estimated that one-third of these are of Portuguese heritage.

Symptoms of GAMT deficiency often present from infancy up to 3 years of age and are more severe in organs and tissues that need a large amount of energy, such as the brain. It is characterised by mild to severe intellectual disability and a delay in reaching developmental milestones. Individuals may lose acquired skills such as sitting without support. Intellectual disability is linked with speech delay and behavioural problems. Without early treatment, neurological symptoms are often severe. Symptoms include speech delay/limited speech, involuntary movements, and autistic spectrum disorders/ADHD which affect communication or self-injury. Epilepsy is seen in most cases, and many different seizure types are included. Severity of seizures ranges from occasional to those unresponsive to antiepileptic medications.

Diagnosis is often made after the onset of symptoms. Blood and urine tests reveal high Guanidinoacetate levels and low creatine levels in the brain. Diagnosis is confirmed by genetic testing. Early diagnosis leads to more favourable outcomes.

Treatment includes high doses of oral creatine monohydrate along with ornithine supplements and/or dietary restriction of arginine. Dietary changes will be made following appointments with a specialist dietitian and changes to diet must not be made without first discussing it with them. Regular follow-ups are required. Treatment improves some symptoms but is unable to reverse prior intellectual disability and developmental delay. Although GAMT Deficiency is a treatable disorder life expectancy is limited, particularly in those who have complex multiple disabilities and severe seizures.

Humans have chromosomes composed of DNA. Genes are pieces of DNA that carry the genetic instruction. Each chromosome may have several thousand genes. We inherit particular chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.

This is an inherited condition. There is nothing that could have been done to prevent it.

Everyone has a pair of genes that make the guanidinoacetate methyltransferase enzyme. If you have this disorder, neither of these genes works correctly. One non-working gene is inherited from each parent. Parents of those with GAMT Deficiency are carriers of the condition. Carriers do not have the disorder because the other gene of this pair is working correctly

When both parents are carriers, in each pregnancy the risk to the baby is as follows:

• 25% chance (1 in 4) of inheriting the disorder
• 50% chance (1 in 2) for the baby to be a carrier
• 25% chance (1 in 4) for the baby to have two working genes and neither have the disorder nor be a carrier

All information accurately referenced by Metabolic Support UK, however, should you require access to our references, please contact us by email: contact@metabolicsupportuk.org